1
|
Yarur AJ, Chiorean MV, Panés J, Jairath V, Zhang J, Rabbat CJ, Sandborn WJ, Vermeire S, Peyrin-Biroulet L. Achievement of Clinical, Endoscopic, and Histological Outcomes in Patients with Ulcerative Colitis Treated with Etrasimod, and Association with Faecal Calprotectin and C-reactive Protein: Results From the Phase 2 OASIS Trial. J Crohns Colitis 2024; 18:885-894. [PMID: 38245818 PMCID: PMC11147797 DOI: 10.1093/ecco-jcc/jjae007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Revised: 12/20/2023] [Accepted: 01/19/2024] [Indexed: 01/22/2024]
Abstract
BACKGROUND AND AIMS Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis [UC]. This post-hoc analysis of the phase 2 OASIS trial [NCT02447302] evaluated its efficacy for endoscopic improvement-histologic remission [EIHR] and assessed correlation between faecal calprotectin [FCP] and C-reactive protein [CRP] levels with efficacy outcomes. METHODS In total, 156 adults with moderately to severely active UC received once-daily etrasimod (1 mg [n = 52]; 2 mg [n = 50]) or placebo [n = 54] for 12 weeks. Clinical, endoscopic, and histologic variables were evaluated at baseline and Week 12. EIHR was defined as achievement of endoscopic improvement [endoscopic subscore ≤ 1, without friability] and histologic remission [Geboes score < 2.0]. Outcomes included the relationships between FCP and CRP concentration and clinical, endoscopic, and histologic variables. RESULTS Achievement of EIHR was significantly higher in patients who received etrasimod 2 mg versus placebo [19.5% vs 4.1%; Mantel-Haenszel estimated difference, 15.4%; p = 0.010]. In the etrasimod 2 mg group, median FCP and CRP levels at Week 12 were significantly lower in patients who achieved clinical remission, endoscopic improvement, histologic remission, and EIHR versus patients who did not [all p < 0.05]. An FCP concentration cutoff of 250 µg/g achieved optimum sensitivity and specificity for efficacy, including EIHR [0.857 and 0.786, respectively; κ coefficient, 0.3584]. Higher proportions of patients with FCP ≤ 250 µg/g achieved efficacy outcomes at Week 12 versus patients with FCP > 250 µg/g. CONCLUSIONS Etrasimod was effective for inducing EIHR in patients with UC. FCP and CRP may be useful, noninvasive biomarkers to monitor treatment response. CLINICALTRIALS.GOV NUMBER NCT02447302.
Collapse
Affiliation(s)
| | | | - Julián Panés
- Hospital Clinic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain
| | | | - Jinkun Zhang
- Arena Pharmaceuticals, Inc, San Diego, CA, USA, a wholly owned subsidiary of Pfizer Inc, New York, NY, USA
| | - Christopher J Rabbat
- Arena Pharmaceuticals, Inc, San Diego, CA, USA, a wholly owned subsidiary of Pfizer Inc, New York, NY, USA
| | | | | | - Laurent Peyrin-Biroulet
- INSERM, NGERE, University of Lorraine, F54000 Nancy, France
- Groupe Hospitalier Privé Ambroise Paré – Hartmann, Paris IBD Center, 92200 Neuilly-sur-Seine, France
| |
Collapse
|
2
|
Characteristics and Effect of Anxiety and Depression Trajectories in Inflammatory Bowel Disease. Am J Gastroenterol 2023; 118:304-316. [PMID: 36227779 DOI: 10.14309/ajg.0000000000002063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Accepted: 10/06/2022] [Indexed: 11/25/2022]
Abstract
INTRODUCTION Symptoms of common mental disorders, such as anxiety or depression, are associated with adverse clinical outcomes in inflammatory bowel disease (IBD). We report trajectories of these symptoms in IBD, patient characteristics associated with different trajectories, and effects on healthcare utilization and prognosis. METHODS We collected demographic, symptom, psychological, and quality-of-life data, with questionnaires at 3-month intervals, over 12 months of follow-up. We collected healthcare utilization and IBD outcomes through notes review. We compared characteristics of those with persistently normal or improving anxiety or depression scores with those with persistently abnormal or worsening scores and the number of flares, glucocorticosteroid prescriptions, escalations of therapy, hospitalizations, or intestinal resections due to IBD activity. RESULTS Among 771 and 777 patients, respectively, worsening or persistently abnormal anxiety or depression scores were associated with increased antidepressant (28.6% vs 12.3% anxiety, 35.8% vs 10.1% depression, P < 0.001) and opiate use (19.0% vs 7.8% anxiety, P = 0.001 and 34.0% vs 7.4% depression, P < 0.001), compared with those with persistently normal or improving scores. These individuals were also more likely to have been diagnosed with IBD in the last 12 months (16.3% vs 5.0% anxiety, P = 0.001, and 15.1% vs 5.5% depression, P = 0.006), to have clinically active disease at baseline (57.1% vs 26.6% anxiety and 71.7% vs 29.1% depression, P < 0.001) and lower quality-of-life scores ( P < 0.001). Individuals with worsening or persistently abnormal trajectories of anxiety or depression required significantly more outpatient appointments, radiological investigations, and endoscopic procedures for IBD-related symptoms. DISCUSSION In this 12-month follow-up study, patients with IBD with worsening or persistently high anxiety or depression scores were higher utilizers of health care but were not at an increased risk of future adverse disease outcomes.
Collapse
|
3
|
Freitas M, de Castro FD, Macedo Silva V, Arieira C, Cúrdia Gonçalves T, Leite S, Moreira MJ, Cotter J. Ultrasonographic scores for ileal Crohn's disease assessment: Better, worse or the same as contrast-enhanced ultrasound? BMC Gastroenterol 2022; 22:252. [PMID: 35585503 PMCID: PMC9118849 DOI: 10.1186/s12876-022-02326-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Accepted: 04/27/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Intestinal ultrasound (IUS) is an increasingly used non-invasive tool to evaluate Crohn's disease (CD) activity. Recently, two IUS scores that evaluate inflammatory activity have emerged: the Simple Ultrasound Activity Score for CD (SUS-CD) and the International Bowel Ultrasound Segmental Activity Score (IBUS-SAS). We aimed to compare the accuracy of SUS-CD, IBUS-SAS and contrast-enhanced ultrasound (CEUS) in predicting inflammatory activity in the terminal ileum in ileocolonoscopy in CD patients. METHODS Retrospective study including all consecutive CD patients submitted to IUS with CEUS directed to the terminal ileum performed by a single operator between April 2016 and March 2020. Segmental SUS-CD and IBUS-SAS were calculated. A time-intensity curve of the contrast bowel wall enhancement was created with measurement of peak intensity using CEUS. The CD endoscopic activity in ileocolonoscopy was graded by Simple Endoscopic Score for CD (SES-CD) as inactive (SES-CD < 7) or active (SES-CD ≥ 7). RESULTS Fifty patients were included, 54.0% were female, with mean age of 34 ± 12 years, and most had isolated ileal disease (60.0%), and a nonstricturing, nonpenetrating behaviour (44.0%). Most of the patients (60.0%) had active endoscopic disease (SES-CD ≥ 7). SUS-CD and IBUS-SAS were not different between patients with active or inactive endoscopic disease (p = 0.15; 0.57, respectively), having a poor accuracy to correlate endoscopic activity (area under de curve (AUC) 0.62; 0.55, respectively). Peak intensity in CEUS was significantly different in patients with active or inactive endoscopic disease (p = 0.004), having a good accuracy to correlate endoscopic activity (AUC 0.80). CONCLUSION Unlike CEUS, SUS-CD and IBUS-SAS were not able to accurately correlate endoscopic activity in terminal ileum in CD. Therefore, CEUS is a non-invasive emerging method that should be increasingly integrated in the ultrasonographic evaluation of CD patients.
Collapse
Affiliation(s)
- M Freitas
- Gastroenterology Department, Hospital da Senhora da Oliveira, Guimarães, Portugal. .,Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal. .,ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal.
| | - F Dias de Castro
- Gastroenterology Department, Hospital da Senhora da Oliveira, Guimarães, Portugal.,Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.,ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - V Macedo Silva
- Gastroenterology Department, Hospital da Senhora da Oliveira, Guimarães, Portugal.,Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.,ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - C Arieira
- Gastroenterology Department, Hospital da Senhora da Oliveira, Guimarães, Portugal.,Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.,ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - T Cúrdia Gonçalves
- Gastroenterology Department, Hospital da Senhora da Oliveira, Guimarães, Portugal.,Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.,ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - S Leite
- Gastroenterology Department, Hospital da Senhora da Oliveira, Guimarães, Portugal.,Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.,ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - M J Moreira
- Gastroenterology Department, Hospital da Senhora da Oliveira, Guimarães, Portugal.,Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.,ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - J Cotter
- Gastroenterology Department, Hospital da Senhora da Oliveira, Guimarães, Portugal.,Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.,ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal
| |
Collapse
|
4
|
Medical Treatment of Intestinal Crohn's disease. SEMINARS IN COLON AND RECTAL SURGERY 2022. [DOI: 10.1016/j.scrs.2022.100862] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
|
5
|
Alfwuaires MA, Algefare AI, Afkar E, Salam SA, El-Moaty HIA, Badr GM. Immunomodulatory assessment of Portulaca oleracea L. extract in a mouse model of colitis. Biomed Pharmacother 2021; 143:112148. [PMID: 34560553 DOI: 10.1016/j.biopha.2021.112148] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 08/23/2021] [Accepted: 08/31/2021] [Indexed: 02/07/2023] Open
Abstract
Ulcerative colitis (UC) is a gastrointestinal inflammatory disease with a multifactorial pathophysiology. This study aims to investigate the immunomodulatory effect of Portulaca oleracea leaf ethanolic extract (POE) on acetic acid (AA)-induced UC in mice. Experimental animals received oral doses of POE (200 mg/kg for 7 days) after an induction of colitis by intrarectal AA administration. In mice with AA-induced UC treated with POE, the results revealed a significant modulation in body weight and colon length. Moreover, treatment with POE downregulated the interleukin 1, 6, and 17, tumor necrosis factor-alpha, gamma interferon, and nuclear factor-kappa B levels compared with the colitis group. Furthermore, POE markedly inhibited histological damage, decreased myeloperoxidase activity and reduced fecal calprotectin level compared with the colitis group. These data are consistent with the reduction in total bacterial content in the colon. Taken together, treatment with POE may reduce colonic inflammation by alleviating the immune response and inhibiting the severity of colitis. The HPLC analysis of POE resulted in the identification of seven medicinal compounds comprising two phenolic acids (ferulic and caffeic acids) and five flavonoids (kaempferol, quercetin, rutin, narenginin and hesperidin). Subsequent analysis of POE by GC-MS revealed ten phytocomponents; the major percentages were hexadecenoic acid, methyl ester (29.8119%), α-linolenic acid (25.8431%), 16-octadecenoic acid, methyl ester (15.1578%) and α-tocopherol (10.7848%). Delta-lactams and alkanes were the minor components. Such natural plant-derived substances and their probable synergistic action appear to contribute to a promising therapeutic protocol for colitis.
Collapse
Affiliation(s)
- Manal A Alfwuaires
- Department of Biological Sciences, Faculty of Science, King Faisal University, P.O. Box 380, Al-Ahsa 31982, Saudi Arabia.
| | - Abdulmohsen I Algefare
- Department of Biological Sciences, Faculty of Science, King Faisal University, P.O. Box 380, Al-Ahsa 31982, Saudi Arabia.
| | - Eman Afkar
- Department of Biological Sciences, Faculty of Science, King Faisal University, P.O. Box 380, Al-Ahsa 31982, Saudi Arabia; Department of Botany and Microbiology, College of Science, Beni-Suef University, Beni-Suef 62511, Egypt.
| | - Sherine Abdel Salam
- Department of Zoology, Faculty of Science, Alexandria University, Alexandria 21511, Egypt.
| | - Heba Ibrahim Abd El-Moaty
- Department of Biological Sciences, Faculty of Science, King Faisal University, P.O. Box 380, Al-Ahsa 31982, Saudi Arabia; Medicinal and Aromatic Plants Department, Desert Research Center El-Mataria, Cairo 11753, Egypt.
| | - Gehan M Badr
- Department of Biological Sciences, Faculty of Science, King Faisal University, P.O. Box 380, Al-Ahsa 31982, Saudi Arabia; Department of Zoology, Faculty of Science, Ain Shams University, Cairo 11566, Egypt.
| |
Collapse
|
6
|
Yagi S, Furukawa S, Shiraishi K, Hashimoto Y, Tange K, Mori K, Ninomiya T, Suzuki S, Shibata N, Murakami H, Ohashi K, Hasebe A, Tomida H, Yamamoto Y, Takeshita E, Ikeda Y, Hiasa Y. Effect of disease duration on the association between serum albumin and mucosal healing in patients with ulcerative colitis. BMJ Open Gastroenterol 2021; 8:bmjgast-2021-000662. [PMID: 34099464 PMCID: PMC8186756 DOI: 10.1136/bmjgast-2021-000662] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Accepted: 05/18/2021] [Indexed: 12/18/2022] Open
Abstract
Objective Serum albumin is used as a marker of acute inflammation. Several studies have addressed the association between serum albumin and clinical outcome in patients with ulcerative colitis (UC). While mucosal healing (MH) has been indicated as the therapeutic goal for UC, the association between serum albumin and MH remains unclear. We evaluated this issue in patients with UC overall and explored whether duration of UC affected this association. Design This cross-sectional study recruited consecutive patients with UC. Study subjects consisted of 273 Japanese patients with UC. Serum albumin was divided into tertiles based on its distribution in all study subjects. One endoscopy specialist was responsible for measuring partial MH and MH, which were defined as a Mayo endoscopic subscore of 0–1 and 0, respectively. The association between serum albumin and clinical outcomes was assessed by multivariate logistic regression. Results Rates of clinical remission, partial MH and MH were 57.9%, 63% and 26%, respectively. Only high serum albumin (>4.4 mg/dL) was significantly positively associated with MH (OR 2.29 (95% CI: 1.03 to 5.29), p for trend=0.043). In patients with short UC duration (<7 years) only, high serum albumin was significantly positively associated with MH and clinical remission. In patients with long UC duration (≥7 years), in contrast, no association between serum albumin and clinical outcomes was found. Conclusion In Japanese patients with UC, serum albumin was significantly positively associated with MH. In patients with short UC duration, serum albumin might be a useful complementary marker for MH.
Collapse
Affiliation(s)
- Sen Yagi
- Department of Internal Medicine, Saiseikai Matsuyama Hospital, Matsuyama, Japan
| | | | - Kana Shiraishi
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Yu Hashimoto
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Kazuhiro Tange
- Department of Inflammatory Bowel Diseases and Therapeutics, Ehime University Graduate School of Medicine, Toon, Japan
| | | | - Tomoyuki Ninomiya
- Department of Gastroenterology, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Seiyuu Suzuki
- Department of Gastroenterology, Sumitomo Besshi Hospital, Niihama, Japan
| | - Naozumi Shibata
- Department of Gastroenterology, Ehime Prefectural Niihama Hospital, Niihama, Japan
| | - Hidehiro Murakami
- Department of Internal Medicine, Saiseikai Matsuyama Hospital, Matsuyama, Japan
| | - Katsuhisa Ohashi
- Ohashi Clinic participate in Gastro-Enterology and Ano-Proctology, Niihama, Japan
| | | | - Hideomi Tomida
- Endoscopy Center, Ehime University Hospital, Toon, Japan
| | | | - Eiji Takeshita
- Department of Inflammatory Bowel Diseases and Therapeutics, Ehime University Graduate School of Medicine, Toon, Japan
| | - Yoshio Ikeda
- Endoscopy Center, Ehime University Hospital, Toon, Japan
| | - Yoichi Hiasa
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| |
Collapse
|
7
|
Wright E. Non-invasive biomarkers as treatment targets: What do we all need to know? J Gastroenterol Hepatol 2021; 36 Suppl 1:12-13. [PMID: 33817840 DOI: 10.1111/jgh.15449] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Affiliation(s)
- Emily Wright
- St Vincent's Hospital, University of Melbourne, Melbourne, Victoria, Australia
| |
Collapse
|
8
|
Zou F, Wang X, Glitza Oliva IC, McQuade JL, Wang J, Zhang HC, Thompson JA, Thomas AS, Wang Y. Fecal calprotectin concentration to assess endoscopic and histologic remission in patients with cancer with immune-mediated diarrhea and colitis. J Immunother Cancer 2021; 9:jitc-2020-002058. [PMID: 33436487 PMCID: PMC7805368 DOI: 10.1136/jitc-2020-002058] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/20/2020] [Indexed: 12/23/2022] Open
Abstract
Background Immune-mediated diarrhea and colitis (IMDC) is currently diagnosed and monitored by evaluating clinical symptoms. Deep remission is determined by endoscopic and histologic evaluation of the disease process. However, repeating these invasive procedures frequently can become cumbersome. We sought to assess the role of fecal calprotectin (FC) concentration as a non-invasive biomarker of endoscopic or histologic remission. Methods We performed a retrospective study of patients with IMDC who were tested for FC at IMDC onset and after IMDC treatment between June 2016 and March 2020. Patient demographics, clinical variables, and FC data were collected and analyzed to determine the optimal cut-off FC concentration to predict endoscopic and histologic remission. Results Our sample comprised 77 patients with a median age of 62 years; 66% were male and 94% were Caucasian. Sixty-five patients (84%) achieved clinical remission, 46 (60%) achieved endoscopic remission, and 24 (31%) achieved histologic remission after IMDC treatment. FC concentrations decreased from the time of IMDC onset to the end of treatment (p<0.001). High FC concentrations were associated with evident endoscopic inflammation (p=0.003) and acute/chronic active colitis (p=0.025) which positively correlated with the Mayo Endoscopic Subscore (r=0.615, p=0.001) at the time of IMDC onset. In patients who achieved endoscopic remission after treatment, a significantly lower FC concentration was observed at IMDC onset (p=0.006) and after treatment (p<0.001) compared with those without endoscopic remission. The cut-off FC concentration to predict endoscopic remission was ≤116 μg/g and for histologic remission ≤80 μg/g; these cut-offs had optimal specificity (94% and 85%, respectively) and positive predictive value (0.91 and 0.38, respectively). Conclusions FC concentration may serve as a non-invasive biomarker to predict endoscopic and histologic remission in patients receiving treatment for IMDC, minimizing the need for frequent invasive endoscopies. Future prospective studies are needed to provide further insight on the role of this marker in disease surveillance.
Collapse
Affiliation(s)
- Fangwen Zou
- Department of Oncology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
- Department of Gastroenterology, Hepatology and Nutrition, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Xuemei Wang
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Isabella C Glitza Oliva
- Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Jennifer L McQuade
- Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Jennifer Wang
- Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Hao Chi Zhang
- Department of Gastroenterology, Hepatology and Nutrition, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - John A Thompson
- University of Washington, Seattle Cancer Care Alliance, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
| | - Anusha S Thomas
- Department of Gastroenterology, Hepatology and Nutrition, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Yinghong Wang
- Department of Gastroenterology, Hepatology and Nutrition, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| |
Collapse
|
9
|
Reinisch W, Gecse K, Halfvarson J, Irving PM, Jahnsen J, Peyrin-Biroulet L, Rogler G, Schreiber S, Danese S. Clinical Practice of Adalimumab and Infliximab Biosimilar Treatment in Adult Patients With Crohn's Disease. Inflamm Bowel Dis 2021; 27:106-122. [PMID: 32634212 PMCID: PMC7737159 DOI: 10.1093/ibd/izaa078] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Indexed: 12/16/2022]
Abstract
The introduction of tumor necrosis factor (TNF) inhibitors has significantly changed the treatment landscape in Crohn's disease (CD). The overall therapeutic achievements with TNF inhibitors such as infliximab, adalimumab, and certolizumab pegol paved the way to push the boundaries of treatment goals beyond symptomatic relief and toward cessation of objective signs of inflammation, including endoscopic remission. Even though these agents are widely used for the treatment of moderate to severe CD, heterogeneity still exists in translating evidence-based guidelines on the use of anti-TNF agents into actual treatment algorithms in CD. This might be due to several reasons including disparities in health expenditure policies; lack of harmonization between countries; and variations in assessment of disease severity, use of disease monitoring tools, or application of treatment targets by physicians. With the advent of biosimilars, patent-free versions of reference biologics are now available to minimize health inequalities in drug availability. In this context, this article aims to provide practical clinical guidance for the use of infliximab and adalimumab biosimilars in patients with moderate to severe CD by outlining different clinical scenarios that patients may encounter during their treatment journey.
Collapse
Affiliation(s)
- Walter Reinisch
- Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
| | - Krisztina Gecse
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam University Medical Center, Amsterdam, the Netherlands
| | - Jonas Halfvarson
- Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Peter M Irving
- Department of Gastroenterology, Guy’s and St. Thomas’ NHS Foundation Trust, London, UK
| | - Jørgen Jahnsen
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway
| | - Laurent Peyrin-Biroulet
- Department of Hepato-Gastroenterology and Inserm U954, University Hospital of Nancy, Lorraine University, Vandoeuvre-lès-Nancy, France
| | - Gerhard Rogler
- Department of Gastroenterology and Hepatology, University Hospital, University of Zurich, Zurich, Switzerland
| | - Stefan Schreiber
- Institute of Clinical Molecular Biology, Christian-Albrechts-Universität zu Kiel, Kiel, Germany
- Clinic of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany
| | - Silvio Danese
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Center, Milan, Italy
| |
Collapse
|
10
|
Lamers CR, de Roos NM, Bongers CCWG, Ten Haaf DSM, Hartman YAW, Witteman BJM, Hopman MTE. Repeated prolonged moderate-intensity walking exercise does not appear to have harmful effects on inflammatory markers in patients with inflammatory bowel disease. Scand J Gastroenterol 2021; 56:30-37. [PMID: 33211989 DOI: 10.1080/00365521.2020.1845791] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND OBJECTIVES The role of exercise in the management of inflammatory bowel disease (IBD) is inconclusive as most research focused on short or low-intensity exercise bouts and subjective outcomes. We assessed the effects of repeated prolonged moderate-intensity exercise on objective inflammatory markers in IBD patients. METHODS In this study, IBD patients (IBD walkers, n = 18), and a control group (non-IBD walkers, n = 19), completed a 30, 40 or 50 km walking exercise on four consecutive days. Blood samples were taken at baseline and every day post-exercise to test for the effect of disease on exercise-induced changes in cytokine concentrations. A second control group of IBD patients who did not take part in the exercise, IBD non-walkers (n = 19), was used to test for the effect of exercise on faecal calprotectin. Both IBD groups also completed a clinical disease activity questionnaire. RESULTS Changes in cytokine concentrations were similar for IBD walkers and non-IBD walkers (IL-6 p = .95; IL-8 p = .07; IL-10 p = .40; IL-1β p = .28; TNF-α p = .45), with a temporary significant increase in IL-6 (p < .001) and IL-10 (p = .006) from baseline to post-exercise day 1. Faecal calprotectin was not affected by exercise (p = .48). Clinical disease activity did not change in the IBD walkers with ulcerative colitis (p = .92), but did increase in the IBD walkers with Crohn's disease (p = .024). CONCLUSION Repeated prolonged moderate-intensity walking exercise led to similar cytokine responses in participants with or without IBD, and it did not affect faecal calprotectin concentrations, suggesting that IBD patients can safely perform this type of exercise.
Collapse
Affiliation(s)
- Carlijn R Lamers
- Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, The Netherlands.,Department of Gastroenterology and Hepatology, Hospital Gelderse Vallei, Ede, The Netherlands
| | - Nicole M de Roos
- Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, The Netherlands
| | - Coen C W G Bongers
- Department of Physiology, Radboud University Medical Center, Nijmegen, The Netherlands
| | | | - Yvonne A W Hartman
- Department of Physiology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Ben J M Witteman
- Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, The Netherlands.,Department of Gastroenterology and Hepatology, Hospital Gelderse Vallei, Ede, The Netherlands
| | - Maria T E Hopman
- Department of Physiology, Radboud University Medical Center, Nijmegen, The Netherlands
| |
Collapse
|
11
|
Rodrigues BL, Mazzaro MC, Nagasako CK, Ayrizono MDLS, Fagundes JJ, Leal RF. Assessment of disease activity in inflammatory bowel diseases: Non-invasive biomarkers and endoscopic scores. World J Gastrointest Endosc 2020; 12:504-520. [PMID: 33362904 PMCID: PMC7739141 DOI: 10.4253/wjge.v12.i12.504] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 10/06/2020] [Accepted: 11/05/2020] [Indexed: 02/05/2023] Open
Abstract
Inflammatory bowel diseases (IBD) comprise two major forms: Crohn's disease and ulcerative colitis. The diagnosis of IBD is based on clinical symptoms combined with results found in endoscopic and radiological examinations. In addition, the discovery of biomarkers has significantly improved the diagnosis and management of IBD. Several potential genetic, serological, fecal, microbial, histological and immunological biomarkers have been proposed for IBD, and they have been evaluated for clinical routine and clinical trials. Ileocolonoscopy, especially with biopsy collection, has been considered the standard method to diagnose IBD and to assess clinical activity of the disease, but it is limited to the colon and terminal ileum and is considered invasive. For this reason, non-invasive biomarkers are necessary for this type of chronic inflammatory disease, which affects mostly young individuals, as they are expected to have a long follow-up.
Collapse
Affiliation(s)
- Bruno Lima Rodrigues
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-878, São Paulo, Brazil
| | - Márcia Carolina Mazzaro
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-878, São Paulo, Brazil
| | - Cristiane Kibune Nagasako
- Department of Gastroenterology, Gastrocenter, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-878, São Paulo, Brazil
| | - Maria de Lourdes Setsuko Ayrizono
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-878, São Paulo, Brazil
| | - João José Fagundes
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-878, São Paulo, Brazil
| | - Raquel Franco Leal
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-878, São Paulo, Brazil
| |
Collapse
|
12
|
The role of fecal calprotectin in the diagnosis of acute pouchitis following IPAA for ulcerative colitis: a systematic clinical review. Int J Colorectal Dis 2020; 35:1619-1628. [PMID: 32617664 DOI: 10.1007/s00384-020-03669-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/10/2020] [Indexed: 02/07/2023]
Abstract
PURPOSE Total proctocolectomy (TPC) with ileal pouch anal anastomosis (IPAA) is commonly performed for patients with refractory ulcerative colitis (UC). Pouchitis occurs in 20-50% of these patients. Fecal calprotectin is a biomarker that correlates well with the pouchitis disease activity index. However, its role in the diagnosis and management of acute pouchitis has not been thoroughly defined. The aim of this study is to review previously established cut-off values and contextualize the clinical utility of fecal calprotectin. METHODS Search of Medline, EMBASE, CENTRAL, and PubMed was performed. Articles were eligible if they measured fecal calprotectin in the setting of pouchitis in patients who underwent TPC with IPAA for UC. Risk of bias of the included studies was evaluated with the QUADAS-2. RESULTS From 117 relevant citations, seven studies with 256 patients (44.8% female, 39.88 years) met inclusion criteria. The pooled prevalence of pouchitis was 42%. The derived fecal calprotectin cut-off values ranged from 56 to 494 μg/g. The corresponding sensitivities and specificities ranged from 57 to 100% and 38 to 92%, respectively. The area under the curve was reported in three studies and ranged from 0.832 to 0.840. CONCLUSION Fecal calprotectin may be a reliable diagnostic tool for acute pouchitis in patients following TPC with IPAA for UC. The high sensitivity of fecal calprotectin for detection of pouchitis makes it a valuable test for ruling out pouchitis. When used in conjunction with other biomarkers, the high specificity offers value in ruling in pouchitis. However, given the complexity of this disease process, relying solely on biomarkers for diagnosis is currently unreasonable.
Collapse
|
13
|
Sævik F, Eriksen R, Eide GE, Gilja OH, Nylund K. Development and Validation of a Simple Ultrasound Activity Score for Crohn's Disease. J Crohns Colitis 2020; 15:115-124. [PMID: 32504533 PMCID: PMC7805799 DOI: 10.1093/ecco-jcc/jjaa112] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND AND AIMS To improve management of patients with Crohn's disease, objective measurements of disease activity are needed. Ileocolonoscopy is the current reference standard but has limitations that restrict repeated use. Ultrasonography is potentially useful for activity monitoring, but no validated sonographic activity index is currently in widespread use. Thus, we aimed to construct and validate a simple ultrasound score for Crohn's disease. METHODS Forty patients were prospectively examined with ultrasound and endoscopy in the development phase. The Simple Endoscopic Score for Crohn's Disease [SES-CD] was used as a reference standard. Seven ultrasound variables [bowel wall thickness, length, colour Doppler, stenosis, fistula, stratification and fatty wrapping] were initially included, and multiple linear regression was used to select the variables that should be included in the final score. Second, the ultrasound data from each patient were re-examined for interobserver assessment using weighted kappa and intraclass correlation. Finally, the activity index was validated in a new cohort of 124 patients. RESULTS Length, fistula and stenosis were excluded. The combination of the remaining variables provided a multiple correlation coefficient of r = 0.78. Interobserver analysis revealed poor agreement for stratification and fatty wrapping and these were thus excluded. There was excellent interobserver agreement for the remaining score consisting of wall thickness and colour Doppler. In both patient cohorts, the ultrasound score correlated well with SES-CD [Development cohort: rho = 0.83, p < 0.001, Validation cohort: rho = 0.78, p < 0.001]. A receiver operating characteristic curve analysis revealed an area under the curve of 0.92 and 0.88 for detecting endoscopic activity and moderate endoscopic activity, respectively. CONCLUSIONS A simple ultrasound activity index for Crohn's disease consisting of bowel wall thickness and colour Doppler was constructed and validated and correlated well with endoscopic disease activity.ClinicalTrials. gov ID: NCT03481751.
Collapse
Affiliation(s)
- Fredrik Sævik
- Department of Clinical Medicine, University of Bergen, Bergen, Norway,National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway,Corresponding author: Fredrik Sævik, MD, Department of Clinical Medicine, University of Bergen, Haukeland University Hospital, Jonas Lies vei, N-5021 Bergen, Norway. Tel: +47 40 01 39 10; Fax: + 47 55 97 29 50;
| | - Ragnar Eriksen
- Department of Medicine, Ålesund Hospital, Ålesund, Norway
| | - Geir Egil Eide
- Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway,Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway
| | - Odd Helge Gilja
- Department of Clinical Medicine, University of Bergen, Bergen, Norway,National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway
| | - Kim Nylund
- Department of Clinical Medicine, University of Bergen, Bergen, Norway,National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway
| |
Collapse
|
14
|
Krzystek-Korpacka M, Kempiński R, Bromke M, Neubauer K. Biochemical Biomarkers of Mucosal Healing for Inflammatory Bowel Disease in Adults. Diagnostics (Basel) 2020; 10:E367. [PMID: 32498475 PMCID: PMC7344443 DOI: 10.3390/diagnostics10060367] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Revised: 05/29/2020] [Accepted: 05/30/2020] [Indexed: 02/06/2023] Open
Abstract
Mucosal healing (MH) is the key therapeutic target of inflammatory bowel disease (IBD). The evaluation of MH remains challenging, with endoscopy being the golden standard. We performed a comprehensive overview of the performance of fecal-, serum-, and urine-based biochemical markers in colonic IBD to find out whether we are ready to replace endoscopy with a non-invasive but equally accurate instrument. A Pubmed, Web of Knowledge, and Scopus search of original articles as potential MH markers in adults, published between January 2009 and March 2020, was conducted. Finally, 84 eligible studies were identified. The most frequently studied fecal marker was calprotectin (44 studies), with areas under the curves (AUCs) ranging from 0.70 to 0.99 in ulcerative colitis (UC) and from 0.70 to 0.94 in Crohn`s disease (CD), followed by lactoferrin (4 studies), matrix metalloproteinase-9 (3 studies), and lipocalin-2 (3 studies). The most frequently studied serum marker was C-reactive protein (30 studies), with AUCs ranging from 0.60 to 0.96 in UC and from 0.64 to 0.93 in CD. Fecal calprotectin is an accurate MH marker in IBD in adults; however, it cannot replace endoscopy and the application of calprotectin is hampered by the lack of standardization concerning the cut-off value. Other markers are either not sufficiently accurate or have not been studied extensively enough.
Collapse
Affiliation(s)
| | - Radosław Kempiński
- Department of Gastroenterology and Hepatology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland;
| | - Mariusz Bromke
- Department of Medical Biochemistry, Wroclaw Medical University, Chalubinskiego 10, 50-368 Wroclaw, Poland;
| | - Katarzyna Neubauer
- Department of Gastroenterology and Hepatology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland;
| |
Collapse
|
15
|
Dulai PS, Jairath V, Khanna R, Ma C, McCarrier KP, Martin ML, Parker CE, Morris J, Feagan BG, Sandborn WJ. Development of the symptoms and impacts questionnaire for Crohn's disease and ulcerative colitis. Aliment Pharmacol Ther 2020; 51:1047-1066. [PMID: 32319120 PMCID: PMC7317756 DOI: 10.1111/apt.15726] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2019] [Revised: 01/03/2020] [Accepted: 03/24/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Patient-reported outcome (PRO) measures historically used in inflammatory bowel disease have been considered inadequate to support future drug labelling claims by regulatory agencies. AIMS To develop PRO tools for use in Crohn's disease (CD) and ulcerative colitis (UC) following guidance issued by the US FDA and the ISPOR (International Society for Pharmacoeconomics and Outcomes Research). METHODS Concept elicitation and cognitive interviews were conducted in adult patients (≥18 years) across the United States and Canada. Semi-structured interview guides were used to collect data, and interview transcripts were coded and analysed. Concept elicitation results were considered alongside existing literature and clinical expert opinion to identify candidate PRO items. Cognitive interviews evaluated concept relevance, interpretability and structure, and facilitated instrument refinement. Concept elicitation participants, except those with an ostomy, underwent centrally read endoscopy to assess inflammatory status. RESULTS In all, 54 participants (mean age: 46.2 years; 66.7% female) were included in the CD concept elicitation interviews. In total, 80 symptom concepts and 61 impact concepts were identified. After three waves of cognitive interviews, the 31-item Symptoms and Impacts Questionnaire for CD (SIQ-CD) was developed. In the UC concept elicitation phase, 53 participants were interviewed (mean age: 41.4 years; 49.1% female). In total, 79 symptoms concepts and 49 impact concepts were identified. Following two waves of cognitive interviews, the 29-item Symptoms and Impacts Questionnaire for UC (SIQ-UC) was developed. Both instruments include four symptom and six impact domains. CONCLUSIONS We developed PROs to support CD and UC drug labelling claims. Psychometric validation studies to evaluate instrument reliability and responsiveness are ongoing.
Collapse
Affiliation(s)
- Parambir S. Dulai
- Robarts Clinical Trials Inc.LondonONCanada
- Division of GastroenterologyUniversity of California, San DiegoLa JollaCAUSA
| | - Vipul Jairath
- Robarts Clinical Trials Inc.LondonONCanada
- Department of MedicineUniversity of Western OntarioLondonONCanada
- Department of Epidemiology and BiostatisticsUniversity of Western OntarioLondonONCanada
| | - Reena Khanna
- Robarts Clinical Trials Inc.LondonONCanada
- Department of MedicineUniversity of Western OntarioLondonONCanada
| | - Christopher Ma
- Robarts Clinical Trials Inc.LondonONCanada
- Division of Gastroenterology and HepatologyDepartments of Medicine and Community Health SciencesUniversity of CalgaryCalgaryABCanada
| | - Kelly P. McCarrier
- Patient‐Centered Outcomes Center of ExcellencePharmerit InternationalBethesdaMDUSA
| | | | | | | | - Brian G. Feagan
- Robarts Clinical Trials Inc.LondonONCanada
- Department of MedicineUniversity of Western OntarioLondonONCanada
- Department of Epidemiology and BiostatisticsUniversity of Western OntarioLondonONCanada
| | - William J. Sandborn
- Robarts Clinical Trials Inc.LondonONCanada
- Division of GastroenterologyUniversity of California, San DiegoLa JollaCAUSA
| |
Collapse
|
16
|
Bertani L, Caviglia GP, Antonioli L, Pellicano R, Fagoonee S, Astegiano M, Saracco GM, Bugianesi E, Blandizzi C, Costa F, Ribaldone DG. Serum Interleukin-6 and -8 as Predictors of Response to Vedolizumab in Inflammatory Bowel Diseases. J Clin Med 2020; 9:jcm9051323. [PMID: 32370274 PMCID: PMC7290461 DOI: 10.3390/jcm9051323] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Revised: 04/24/2020] [Accepted: 04/26/2020] [Indexed: 12/15/2022] Open
Abstract
Vedolizumab, a monoclonal antibody directed against integrin α4β7, is an effective treatment for inflammatory bowel diseases. However, a significant number of patients do not achieve steroid-free clinical remission in the first year of treatment. An early identification of these patients is one of the most important challenges for clinicians and offers the possibility of therapeutic optimization in order to personalize biological therapy. The aim of our study was to test the prediction ability of interleukin (IL)-6 and -8 of clinical response after 12 months of therapy with vedolizumab (T2). We performed a prospective, multicentre study in patients affected by inflammatory bowel disease by analysing cytokines level before starting vedolizumab (T0) and after 10 weeks of therapy (T1). In the overall cohort (n = 54), IL-8 decrease > 2.6 pg/mL in the first 10 weeks of therapy was able to predict clinical response (area under the curve (AUC) = 0.70, sensitivity = 66%, specificity = 75%, p = 0.010), negative C-reactive protein (CRP) (AUC = 0.71, sensitivity = 64%, specificity = 80%, p = 0.009) and calprotectin < 250 mg/kg (AUC = 0.69, sensitivity = 64%, specificity = 78%, p = 0.030) after 44 weeks of therapy. In patients with ulcerative colitis (n = 40), baseline IL-8 values > 8.6 pg/mL and a decrease of IL-6 values > 0.4 pg/mL from T0 to T1 were significant and independent predictors of clinical response after 12 months of vedolizumab therapy (odds ratio (OR) = 6.96, 95% CI 1.27–38.22, p = 0.026 and OR = 7.29, 95% CI 1.42–37.50, p = 0.017, respectively). In patients with Crohn’s disease (n = 14), baseline IL-8 values > 8.6 pg/mL and baseline IL-6 values > 1.6 pg/mL allowed the identification of patients achieving negative CRP at T2 (AUC = 0.75, sensitivity = 74%, specificity = 76%, p < 0.001) and patients with faecal calprotectin values < 250 mg/kg at T2 (AUC = 0.71, sensitivity = 78%, specificity = 63%, p = 0.004). In conclusion, our study highlights a potential clinical role of serum cytokine levels for the prediction of clinical and biochemical steroid-free response in patients treated with vedolizumab.
Collapse
Affiliation(s)
- Lorenzo Bertani
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56100 Pisa, Italy;
| | - Gian Paolo Caviglia
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (G.M.S.); (E.B.)
- Correspondence: (G.P.C.); (D.G.R.); Tel.: +39–011–6333918 (D.G.R.)
| | - Luca Antonioli
- Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy; (L.A.); (C.B.)
| | - Rinaldo Pellicano
- Unit of Gastroenterology, Molinette Hospital, 10126 Turin, Italy; (R.P.); (M.A.)
| | - Sharmila Fagoonee
- Institute of Biostructure and Bioimaging, CNR c/o Molecular Biotechnology Centre, 10126 Turin, Italy;
| | - Marco Astegiano
- Unit of Gastroenterology, Molinette Hospital, 10126 Turin, Italy; (R.P.); (M.A.)
| | - Giorgio Maria Saracco
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (G.M.S.); (E.B.)
| | - Elisabetta Bugianesi
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (G.M.S.); (E.B.)
| | - Corrado Blandizzi
- Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy; (L.A.); (C.B.)
| | - Francesco Costa
- Department of General Surgery and Gastroenterology, IBD Unit, Pisa University Hospital, 56100 Pisa, Italy;
| | - Davide Giuseppe Ribaldone
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (G.M.S.); (E.B.)
- Correspondence: (G.P.C.); (D.G.R.); Tel.: +39–011–6333918 (D.G.R.)
| |
Collapse
|
17
|
Fecal Eosinophil Cationic Protein Is a Diagnostic and Predictive Biomarker in Young Adults with Inflammatory Bowel Disease. J Clin Med 2019; 8:jcm8122025. [PMID: 31756948 PMCID: PMC6947361 DOI: 10.3390/jcm8122025] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2019] [Revised: 11/13/2019] [Accepted: 11/18/2019] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND AND AIMS Fecal biomarkers are important non-invasive markers monitoring disease activity in inflammatory bowel disease (IBD). We compared the significance of fecal eosinophil cationic protein (fECP) and fecal calprotectin (fCal). METHODS fECP and fCal were measured in patients with Crohn's disease (CD, n = 97), ulcerative colitis (UC, n = 53), Clostridioides difficile infection (CDI, n = 9), primary food allergy (PFA, n = 11), pollen-associated food allergy (n = 25) and non-inflammatory controls (n = 78). Results were correlated with clinical and endoscopic IBD activity scores. RESULTS fECP was significantly elevated in CD, UC, CDI and PFA compared to controls. fCal was significantly increased in CD, UC and CDI. fECP had lower diagnostic accuracy than fCal (area under the curve (AUC) = 0.88) in differentiating between endoscopically active and inactive patients with IBD (AUC = 0.77, ROC analysis). In contrast to fCal, fECP correlated negatively with age and levels were also elevated in clinically and endoscopically inactive patients with IBD <45 years (endoscopically inactive IBD vs controls; AUC for fECP = 0.86; AUC for fCal = 0.62). However, in those patients with low inflammatory activity (fCal <250 mg/kg), high fECP indicated the need for treatment modification or surgery (fECP <200 µg/kg = 22%; 200-600 µg/kg = 44%; >600 µg/kg = 82%) at month 48 of follow-up. CONCLUSIONS fECP is a diagnostic and prognostic marker in young patients with IBD in remission.
Collapse
|
18
|
Amara J, Saliba Y, Hajal J, Smayra V, Bakhos JJ, Sayegh R, Fares N. Circadian Rhythm Disruption Aggravates DSS-Induced Colitis in Mice with Fecal Calprotectin as a Marker of Colitis Severity. Dig Dis Sci 2019; 64:3122-3133. [PMID: 31115725 DOI: 10.1007/s10620-019-05675-7] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Accepted: 05/15/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is a chronic immunologically mediated pathology that remains a major health burden. Circadian rhythm disruption leads to a deregulation in the immune system which is a major risk factor for IBD. AIMS Since fecal calprotectin (FC) has been a useful tool for monitoring IBD, we aimed to evaluate the effect of circadian rhythm alteration on gut inflammation status and whether FC is associated with the severity of colitis. METHODS C57BL/6J mice were exposed to circadian shifts for 3 months, and then colitis was induced by 2% dextran sulfate sodium (DSS). Colitis was evaluated according to clinical symptoms and histological scoring. Plasma and intestinal inflammatory and permeability markers as well as fecal and intestinal calprotectin were assessed. RESULTS Circadian shifts aggravated DSS-induced colitis with increased diarrhea, flatulence, and fecal blood associated with decreased colon length. In addition, intestinal cryptic architecture was lost with the presence of increased inflammation, mucosal muscle thickening, and cryptic abscesses. Plasma tumor necrosis factor alpha, interleukin 1 beta, interleukin 6, and C-reactive protein upregulations were paralleled by the deterioration of intestinal permeability. Calprotectin expression and distribution increased in the intestines and feces of shifted animals, and levels highly correlated with the increases in intestinal inflammation and permeability. CONCLUSIONS Circadian rhythm disruption aggravates DSS-induced colitis, whereas fecal and intestinal calprotectin associates with the severity of disease. Calprotectin might be a useful marker and tool for assessing patients at risk of IBD due to lifestyles with disruptive sleep patterns.
Collapse
Affiliation(s)
- Joseph Amara
- Laboratoire de Recherche en Physiologie et Physiopathologie, Pôle Technologie Santé, Faculté de Médecine, Université Saint Joseph, Beirut, Lebanon
| | - Youakim Saliba
- Laboratoire de Recherche en Physiologie et Physiopathologie, Pôle Technologie Santé, Faculté de Médecine, Université Saint Joseph, Beirut, Lebanon
| | - Joelle Hajal
- Laboratoire de Recherche en Physiologie et Physiopathologie, Pôle Technologie Santé, Faculté de Médecine, Université Saint Joseph, Beirut, Lebanon
| | - Viviane Smayra
- Faculté de Médecine, Université Saint Joseph, Beirut, Lebanon
| | - Jules-Joel Bakhos
- Laboratoire de Recherche en Physiologie et Physiopathologie, Pôle Technologie Santé, Faculté de Médecine, Université Saint Joseph, Beirut, Lebanon
| | - Raymond Sayegh
- Faculté de Médecine, Université Saint Joseph, Beirut, Lebanon
| | - Nassim Fares
- Laboratoire de Recherche en Physiologie et Physiopathologie, Pôle Technologie Santé, Faculté de Médecine, Université Saint Joseph, Beirut, Lebanon.
| |
Collapse
|
19
|
Kato J, Yoshida T, Hiraoka S. Prediction of treatment outcome and relapse in inflammatory bowel disease. Expert Rev Clin Immunol 2019; 15:667-677. [PMID: 30873890 DOI: 10.1080/1744666x.2019.1593140] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Prediction of treatment outcome and clinical relapse in patients with inflammatory bowel disease (IBD), either ulcerative colitis (UC) or Crohn's disease (CD), is particularly important because therapeutics for IBD are not always effective and patients in remission could frequently relapse. Because undergoing endoscopy for the purpose is sometimes invasive and burdensome to patients, the performance of surrogate biomarkers has been investigated. Areas covered: We particularly featured the performance of patient symptoms, blood markers including C-reactive protein (CRP), fecal markers including fecal calprotectin (Fcal) and fecal immunochemical test (FIT) for prediction of endoscopic mucosal healing (MH) and prediction of relapse. Studies of other modalities and therapeutic drug monitoring (TDM) have also been explored. Expert opinion: Meticulous evaluation of patient symptoms could be predictive for MH in UC. CRP and Fcal may be accurate in prediction of MH of CD when MH is evaluated throughout the entire intestine including the small bowel. Repeated measurements of fecal markers including Fcal and FIT in patients with clinical remission would raise predictability of relapse. Prediction of treatment outcome by monitoring with blood markers including CRP, fecal markers including Fcal, and TDM has frequently been performed in recent clinical trials and shown to be effective.
Collapse
Affiliation(s)
- Jun Kato
- a Department of Gastroenterology , Mitsui Memorial Hospital , Tokyo , Japan
| | - Takeichi Yoshida
- b Second Department of Internal Medicine , Wakayama Medical University , Wakayama , Japan
| | - Sakiko Hiraoka
- c Department of Gastroenterology and Hepatology , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama , Japan
| |
Collapse
|
20
|
Restellini S, Chao CY, Martel M, Barkun A, Kherad O, Seidman E, Wild G, Bitton A, Afif W, Bessissow T, Lakatos PL. Clinical Parameters Correlate With Endoscopic Activity of Ulcerative Colitis: A Systematic Review. Clin Gastroenterol Hepatol 2019; 17:1265-1275.e8. [PMID: 30583048 DOI: 10.1016/j.cgh.2018.12.021] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2018] [Revised: 12/12/2018] [Accepted: 12/14/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Optimal management of patients with ulcerative colitis (UC) requires assessment of disease activity-usually by endoscopy, which is invasive, costly, and not risk free. We performed a systematic review to determine whether clinical symptoms correlate with findings from endoscopy assessments of patients with UC. METHODS We performed a systematic review of publication databases from January 1980 through July 2018 to identify clinical trials and observational studies reporting correlations among symptoms, disease activity index scores and/or patient reported outcomes (rectal bleeding and/or stool frequency), and endoscopic disease activity. Correlations were ascertained in patients with active vs inactive disease and by disease extent and treatment type. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Because of significant heterogeneity, meta-analysis was not possible. Results were synthesized qualitatively and systematically. RESULTS Our final analysis included 23 studies (1 randomized trial, 22 observational studies) comprising 3320 patients with UC. The studies used a variety of measures to assess clinical activity, endoscopic activity, and measures of correlation (sensitivity, specificity, correlation coefficients, area under the receiver operator curve). Overall, studies were at moderate-high risk of bias. Composite clinical measures, including rectal bleeding and stool frequency, had moderate to strong correlations with endoscopic disease activity; the absence of rectal bleeding identified patients with inactive disease with higher levels of sensitivity than normalization of stool frequency. In general, symptoms correlated more strongly with endoscopic activity in patients with left-sided colitis than extensive colitis. The effect of different medications on the correlation between clinical and endoscopic activity has not been well studied. CONCLUSIONS In a systematic review, we found a moderate to strong correlation between clinical activity, particularly the combination of rectal bleeding and stool frequency, and endoscopic activity in patients with UC. Although these clinical assessments could help prioritize patients for endoscopic evaluation in resource-limited settings, challenges associated with treating patients based on symptoms alone preclude adaptation of current management algorithms.
Collapse
Affiliation(s)
- Sophie Restellini
- Division of Gastroenterology, McGill University Health Centre, Montreal, Canada; Division of Gastroenterology and Hepatology, Geneva's University Hospitals, University of Geneva, Switzerland
| | - Che-Yung Chao
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Australia
| | - Myriam Martel
- Division of Gastroenterology, Epidemiology and Biostatistics and Occupational Health, McGill University Health Centre, Montreal, Canada
| | - Alan Barkun
- Division of Gastroenterology, McGill University Health Centre, Montreal, Canada; Division of Gastroenterology, Epidemiology and Biostatistics and Occupational Health, McGill University Health Centre, Montreal, Canada
| | - Omar Kherad
- Internal Medicine Department, La Tour Hospital, University of Geneva, Switzerland
| | - Ernest Seidman
- Division of Gastroenterology, McGill University Health Centre, Montreal, Canada
| | - Gary Wild
- Division of Gastroenterology, McGill University Health Centre, Montreal, Canada
| | - Alain Bitton
- Division of Gastroenterology, McGill University Health Centre, Montreal, Canada
| | - Waqqas Afif
- Division of Gastroenterology, McGill University Health Centre, Montreal, Canada
| | - Talat Bessissow
- Division of Gastroenterology, McGill University Health Centre, Montreal, Canada
| | - Peter L Lakatos
- Division of Gastroenterology, McGill University Health Centre, Montreal, Canada; First Department of Medicine, Semmelweis University, Budapest, Hungary.
| |
Collapse
|
21
|
Ma C, Battat R, Parker CE, Khanna R, Jairath V, Feagan BG. Update on C-reactive protein and fecal calprotectin: are they accurate measures of disease activity in Crohn's disease? Expert Rev Gastroenterol Hepatol 2019; 13:319-330. [PMID: 30791776 DOI: 10.1080/17474124.2019.1563481] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
'Treat-to-target' paradigms in Crohn's disease (CD) directed at suppressing intestinal inflammation require accurate and reliable measures of disease activity. Although endoscopy has traditionally been considered a gold standard, cost, complexity, resource limitations, and invasiveness are important limitations. Hence, substantial interest exists for non-invasive serum and fecal biomarkers, namely C-reactive protein (CRP) and fecal calprotectin (FC), in the diagnosis, monitoring, and treatment of CD. Areas covered: We review the evidence for using serum CRP and FC in distinguishing patients with CD from those with irritable bowel syndrome, categorizing disease activity among patients with an established diagnosis of CD, predicting the likelihood of treatment response, identifying asymptomatic patients in medically or surgically induced remission who are at risk for disease relapse, and as treatment targets. Expert commentary: Accurate interpretation of CRP and FC is dependent on several factors including the clinical context, the performance characteristics of the assay, the specified test cut-offs, and the pre-test probability of disease. Emerging evidence indicates that CRP and FC are valuable adjuncts for the management of CD in specific circumstances described in this review.
Collapse
Affiliation(s)
- Christopher Ma
- a Division of Gastroenterology and Hepatology , University of Calgary , Calgary , Alberta , Canada.,b Robarts Clinical Trials Inc ., London , Ontario , Canada
| | - Robert Battat
- b Robarts Clinical Trials Inc ., London , Ontario , Canada.,c Division of Gastroenterology , University of California San Diego , La Jolla , CA , USA
| | | | - Reena Khanna
- d Department of Medicine , Western University , London , Ontario , Canada
| | - Vipul Jairath
- b Robarts Clinical Trials Inc ., London , Ontario , Canada.,d Department of Medicine , Western University , London , Ontario , Canada.,e Department of Epidemiology and Biostatistics , Western University , London , Ontario , Canada
| | - Brian Gordon Feagan
- b Robarts Clinical Trials Inc ., London , Ontario , Canada.,d Department of Medicine , Western University , London , Ontario , Canada.,e Department of Epidemiology and Biostatistics , Western University , London , Ontario , Canada
| |
Collapse
|
22
|
What is the role of C-reactive protein and fecal calprotectin in evaluating Crohn's disease activity? Best Pract Res Clin Gastroenterol 2019; 38-39:101602. [PMID: 31327404 DOI: 10.1016/j.bpg.2019.02.004] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2019] [Accepted: 02/14/2019] [Indexed: 02/07/2023]
Abstract
Historically, the evaluation of patients with Crohn's disease (CD) has centered on use of subjective symptom-based assessment. However, patients with CD experience a broad spectrum of non-specific symptoms that may not directly correlate with objective measures of inflammation. Endoscopy has been the gold standard for evaluating the burden and severity of mucosal disease. However, use of ileocolonoscopy for disease monitoring in long-term follow-up is limited by considerations of cost, resource utilization, and invasiveness. As treatment goals in CD have shifted towards 'treat-to-target' paradigms that emphasize tight control of inflammation, it has become increasingly evident that sensitive, accurate, and reliable measures of disease activity are required. The use of non-invasive serum and fecal biomarkers such as C-reactive protein (CRP) and fecal calprotectin (FC) has been evaluated in patients with CD for categorizing disease activity, predicting treatment response, identifying patients at risk for disease relapse, and as a potential therapeutic target. In this review, we summarize the interpretation of CRP and FC in patients with CD within specific clinical contexts and according to assay performance characteristics.
Collapse
|
23
|
Lee YW, Lee KM, Lee JM, Chung YY, Kim DB, Kim YJ, Chung WC, Paik CN. The usefulness of fecal calprotectin in assessing inflammatory bowel disease activity. Korean J Intern Med 2019; 34:72-80. [PMID: 29347813 PMCID: PMC6325438 DOI: 10.3904/kjim.2016.324] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2016] [Accepted: 06/07/2017] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND/AIMS Fecal calprotectin (FC) is known to correlate with disease activity and can be used as a predictor for relapse or treatment response in inflammatory bowel disease (IBD). We evaluated the usefulness of FC as a biomarker for disease activity in patients with IBD using both enzyme-linked immunosorbent assay (ELISA) and a quantitative point-of-care test (QPOCT). METHODS Fecal samples and medical records were collected from consecutive patients with IBD. FC levels were measured by both ELISA and QPOCT and patient medical records were reviewed for clinical, laboratory, and endoscopic data. RESULTS Ninety-three patients with IBD were enrolled, 55 with ulcerative colitis (UC) and 38 with Crohn's disease (CD). The mean FC-ELISA levels were 906.3 ± 1,484.9 μg/g in UC and 1,054.1 ± 1,252.5 μg/g in CD. There was a strong correlation between FC-ELISA level and clinical activity indices (p < 0.05). FC-ELISA level was significantly lower in patients with mucosal healing (MH) compared to those without MH in UC (85.5 ± 55.6 μg/g vs. 1,503.7 ± 2,129.9 μg/g, p = 0.005). The results from the QPOCT corresponded well to those from ELISA. A cutoff value of 201.3 μg/g for FC-ELISA and 150.5 μg/g for FC-QPOCT predicted endoscopic inflammation (Mayo endoscopic subscore ≥ 1) in UC with a sensitivity of 81.8% and 85.8%, respectively, and a specificity of 100% for both. CONCLUSION FC was strongly associated with disease activity indices, serologic markers, and endoscopic activity in patients with IBD. QPOCT can be used more conveniently than ELISA to assess FC in clinical practice.
Collapse
Affiliation(s)
- Yang Woon Lee
- Department of Internal Medicine, College of Medicine, St. Vincent’s Hospital, The Catholic University of Korea, Suwon, Korea
| | - Kang-Moon Lee
- Department of Internal Medicine, College of Medicine, St. Vincent’s Hospital, The Catholic University of Korea, Suwon, Korea
- Correspondence to Kang-Moon Lee, M.D. Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, 93 Jungbu-daero, Paldal-gu, Suwon 16247, Korea Tel: +82-31-249-7138 Fax: +82-31-253-8898 E-mail:
| | - Ji Min Lee
- Department of Internal Medicine, College of Medicine, St. Vincent’s Hospital, The Catholic University of Korea, Suwon, Korea
| | - Yoon Yung Chung
- Department of Internal Medicine, College of Medicine, St. Vincent’s Hospital, The Catholic University of Korea, Suwon, Korea
| | - Dae Bum Kim
- Department of Internal Medicine, College of Medicine, St. Vincent’s Hospital, The Catholic University of Korea, Suwon, Korea
| | - Yeon Ji Kim
- Department of Internal Medicine, College of Medicine, St. Vincent’s Hospital, The Catholic University of Korea, Suwon, Korea
| | - Woo Chul Chung
- Department of Internal Medicine, College of Medicine, St. Vincent’s Hospital, The Catholic University of Korea, Suwon, Korea
| | - Chang-Nyol Paik
- Department of Internal Medicine, College of Medicine, St. Vincent’s Hospital, The Catholic University of Korea, Suwon, Korea
| |
Collapse
|
24
|
Buer LCT, Moum BA, Cvancarova M, Warren DJ, Bolstad N, Medhus AW, Høivik ML. Real world data on effectiveness, safety and therapeutic drug monitoring of vedolizumab in patients with inflammatory bowel disease. A single center cohort. Scand J Gastroenterol 2019; 54:41-48. [PMID: 30650312 DOI: 10.1080/00365521.2018.1548646] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS The efficacy of vedolizumab (VDZ) has been demonstrated in clinical trials. The aim of this report is to evaluate the long-term effectiveness and safety of VDZ in a real-world cohort and to explore possible associations between concentration measurements of VDZ and treatment effectiveness. METHODS This is a prospective clinical follow-up including all adult patients with ulcerative colitis (UC) and Crohn's disease (CD) treated with VDZ from October 2014 until September 2017 at a single center in Norway. The patients were followed for at least 14 weeks or until termination of treatment. Clinical and biochemical activity were obtained at every infusion throughout follow-up. Plasma measurements of VDZ (p-VDZ) were performed before every infusion during maintenance therapy. RESULTS In total, 71 patients received VDZ. Improvement of CRP and hemoglobin was observed in CD but not in UC, whereas Partial Mayo Score improved in UC while no change in Harvey Bradshaw Index was revealed in CD. Furthermore, CRP at baseline was negatively correlated with p-VDZ at week 14 in CD but not in UC patients. CONCLUSION Improvement of biochemical markers of inflammation was observed in CD while clinical activity scores improved in UC patients. For CD, baseline CRP was correlated with lower concentrations of p-VDZ at week 14.
Collapse
Affiliation(s)
- Lydia C T Buer
- a Department of Gastroenterology , Oslo University Hospital , Oslo , Norway.,b Faculty of Medicine , Institute of Clinical Medicine, University of Oslo , Oslo , Norway
| | - Bjørn A Moum
- a Department of Gastroenterology , Oslo University Hospital , Oslo , Norway.,b Faculty of Medicine , Institute of Clinical Medicine, University of Oslo , Oslo , Norway
| | - Milada Cvancarova
- a Department of Gastroenterology , Oslo University Hospital , Oslo , Norway.,c Faculty of Health Sciences , Oslo Metropolitan University , Oslo , Norway
| | - David J Warren
- d Department of Medical Biochemistry , Oslo University Hospital , Oslo , Norway
| | - Nils Bolstad
- b Faculty of Medicine , Institute of Clinical Medicine, University of Oslo , Oslo , Norway.,d Department of Medical Biochemistry , Oslo University Hospital , Oslo , Norway
| | - Asle W Medhus
- a Department of Gastroenterology , Oslo University Hospital , Oslo , Norway
| | - Marte L Høivik
- a Department of Gastroenterology , Oslo University Hospital , Oslo , Norway
| |
Collapse
|
25
|
Fadeeva NA, Korneeva IA, Knyazev OV, Parfenov AI. Biomarkers of inflammatory bowel disease activity. TERAPEVT ARKH 2018; 90:107-111. [DOI: 10.26442/00403660.2018.12.000018] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The review presents data on calprotectin, lactoferrin, leukocytes labeled with isotope indium 111In, calgranulin C and pyruvate kinase type M2 - highly sensitive biomarkers to assess the severity of intestinal inflammation. Their importance in diagnostics, determination of treatment efficiency, including as predictors of recurrence of ulcerative colitis and Crohn's disease is shown.
Collapse
|
26
|
Tsuda S, Kunisaki R, Kato J, Murakami M, Nishio M, Ogashiwa T, Yoshida T, Kimura H, Kitano M. Patient self-reported symptoms using visual analog scales are useful to estimate endoscopic activity in ulcerative colitis. Intest Res 2018; 16:579-587. [PMID: 30301332 PMCID: PMC6223448 DOI: 10.5217/ir.2018.00021] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Accepted: 05/02/2018] [Indexed: 01/17/2023] Open
Abstract
Background/Aims In clinical practice, colonoscopy has been regarded as the gold standard for the evaluation of disease severity as well as mucosal healing in ulcerative colitis (UC). Some activity indices incorporating patient symptoms as parameters have been shown to reflect the endoscopic activity of UC. The aim of this study was to examine whether self-reported symptoms with visual analog scales (VAS) can predict endoscopic activity. Methods A cross-sectional study of 150 UC patients who underwent colonoscopy with submission of VAS scores of 4 symptoms: general condition, bloody stools, stool form, and abdominal pain (0: no symptoms, 10: the most severe symptoms). Each VAS score was compared with colonoscopic activity assessed with the Mayo endoscopic subscore (MES). Results All VAS scores were significantly correlated with the endoscopic severity (Spearman correlation coefficients of general condition, bloody stools, stool form, and abdominal pain: 0.63, 0.64, 0.58, and 0.43, respectively). Mucosal healing defined as MES 0 alone was predicted by VAS score <1.5 on general condition or 0 on bloody stools with sensitivity of 0.84 and 0.76 and specificity of 0.66 and 0.76, respectively. Additionally, VAS score <2.5 on stool form predicted active lesions in distal colorectum alone with sensitivity of 0.67 and specificity of 0.66, suggesting that this item could predict the indication of topical therapy. Conclusions Self-reported VAS scores on symptoms were correlated with endoscopic activity of UC. To clarify the relationship between VAS and mucosal healing, further validation studies are needed.
Collapse
Affiliation(s)
- Saya Tsuda
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Reiko Kunisaki
- Inflammatory Bowel Disease Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Jun Kato
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Mayu Murakami
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Masafumi Nishio
- Inflammatory Bowel Disease Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Tsuyoshi Ogashiwa
- Inflammatory Bowel Disease Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Takeichi Yoshida
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Hideaki Kimura
- Inflammatory Bowel Disease Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Masayuki Kitano
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| |
Collapse
|
27
|
Mumolo MG, Bertani L, Ceccarelli L, Laino G, Di Fluri G, Albano E, Tapete G, Costa F. From bench to bedside: Fecal calprotectin in inflammatory bowel diseases clinical setting. World J Gastroenterol 2018; 24:3681-3694. [PMID: 30197475 PMCID: PMC6127662 DOI: 10.3748/wjg.v24.i33.3681] [Citation(s) in RCA: 120] [Impact Index Per Article: 17.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2018] [Revised: 06/05/2018] [Accepted: 06/27/2018] [Indexed: 02/06/2023] Open
Abstract
Fecal calprotectin (FC) has emerged as one of the most useful tools for clinical management of inflammatory bowel diseases (IBD). Many different methods of assessment have been developed and different cut-offs have been suggested for different clinical settings. We carried out a comprehensive literature review of the most relevant FC-related topics: the role of FC in discriminating between IBD and irritable bowel syndrome (IBS) and its use in managing IBD patients In patients with intestinal symptoms, due to the high negative predictive value a normal FC level reliably rules out active IBD. In IBD patients a correlation with both mucosal healing and histology was found, and there is increasing evidence that FC assessment can be helpful in monitoring disease activity and response to therapy as well as in predicting relapse, post-operative recurrence or pouchitis. Recently, its use in the context of a treat-to-target approach led to a better outcome than clinically-based therapy adjustment in patients with early Crohn’s disease. In conclusion, FC measurement represents a cheap, safe and reliable test, easy to perform and with a good reproducibility. The main concerns are still related to the choice of the optimal cut-off, both for differentiating IBD from IBS, and for the management of IBD patients.
Collapse
Affiliation(s)
- Maria Gloria Mumolo
- Department of General Surgery and Gastroenterology, Gastroenterology Unit, Azienda Ospedaliero Universitaria Pisana, Pisa 56124, Italy
| | - Lorenzo Bertani
- Department of New Technologies and Translational Research in Medicine and Surgery, University of Pisa, Pisa 56122, Italy
| | - Linda Ceccarelli
- Department of General Surgery and Gastroenterology, Gastroenterology Unit, Azienda Ospedaliero Universitaria Pisana, Pisa 56124, Italy
| | - Gabriella Laino
- Department of New Technologies and Translational Research in Medicine and Surgery, University of Pisa, Pisa 56122, Italy
| | - Giorgia Di Fluri
- Department of General Surgery and Gastroenterology, Gastroenterology Unit, Azienda Ospedaliero Universitaria Pisana, Pisa 56124, Italy
| | - Eleonora Albano
- Department of New Technologies and Translational Research in Medicine and Surgery, University of Pisa, Pisa 56122, Italy
| | - Gherardo Tapete
- Department of New Technologies and Translational Research in Medicine and Surgery, University of Pisa, Pisa 56122, Italy
| | - Francesco Costa
- Department of General Surgery and Gastroenterology, Gastroenterology Unit, Azienda Ospedaliero Universitaria Pisana, Pisa 56124, Italy
| |
Collapse
|
28
|
Zhang H, Zeng Z, Mukherjee A, Shen B. Molecular diagnosis and classification of inflammatory bowel disease. Expert Rev Mol Diagn 2018; 18:867-886. [PMID: 30152711 DOI: 10.1080/14737159.2018.1516549] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Traditional diagnosis and classification of inflammatory bowel diseases (IBDs) have been based on clinical evaluation, laboratory testing, endoscopy, imaging, and histological examinations. With the advancement of medical technology, an increasing number of molecular surrogates are playing a key role in diagnosis, differential diagnosis, assessment of disease activity, prediction of clinical course, and therapeutic response of IBD. Areas covered: The authors review roles of both existing and emerging surrogates including genetic, serological, histologic, and fecal markers in diagnosis and classification of IBD. Comparisons in advantages and disadvantages of different markers have also been discussed. In addition, this review underscores controversial and unclear aspects which need further study. Expert commentary: IBD is characteristic of chronicity, relapse-remission and destructiveness. It is of great importance for clinicians to make an accurate diagnosis and classification. Current and new molecular markers perform well with acceptable sensitivity and specificity. The use of molecular markers in clinical practice needs to be further explored and then generalized. More work is warranted to identify novel useful markers and elucidate how to apply them together with current markers in clinical settings.
Collapse
Affiliation(s)
- Hu Zhang
- a Center for Inflammatory Bowel Disease & Department of Gastroenterology , West China Hospital, Sichuan University , Chengdu , China
| | - Zhen Zeng
- a Center for Inflammatory Bowel Disease & Department of Gastroenterology , West China Hospital, Sichuan University , Chengdu , China
| | - Arjudeb Mukherjee
- b West China School of Medicine , Sichuan University , Chengdu , China
| | - Bo Shen
- c Center for Inflammatory Bowel Disease, Digestive Disease and Surgery Institute, The Cleveland Clinic Foundation , Cleveland , Ohio , USA
| |
Collapse
|
29
|
Jha AK, Chaudhary M, Dayal VM, Kumar A, Jha SK, Jha P, Purkayastha S, Ranjan R. Optimal cut-off value of fecal calprotectin for the evaluation of ulcerative colitis: An unsolved issue? JGH OPEN 2018; 2:207-213. [PMID: 30483591 PMCID: PMC6207035 DOI: 10.1002/jgh3.12074] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/08/2018] [Revised: 06/10/2018] [Accepted: 06/23/2018] [Indexed: 12/12/2022]
Abstract
Introduction There is variability in the fecal calprotectin (FCP) cut‐off level for the prediction of ulcerative colitis (UC) disease activity and differentiation from irritable bowel disease (IBS‐D). The FCP cut‐off levels vary from country to country. Aims We aimed to assess FCP as a marker of disease activity in patients with UC. We determined the optimal FCP cut‐off value for differentiating UC and IBS‐D. Methods In a prospective study, we enrolled 76 UC and 30 IBS‐D patients. We studied the correlation of FCP with disease activity/extent as well as its role in differentiating UC from IBS‐D. We also reviewed literature regarding the optimal FCP cut‐off level for the prediction of disease activity and differentiation from IBS‐D patients. Results Sensitivity, specificity, positive predictive value, and negative predictive value of FCP (cut‐off level, 158 μg/g) for the prediction of complete mucosal healing (using Mayo endoscopic subscore) were 90, 85, 94.7, and 73.3%, respectively. Sensitivity, specificity, positive predictive value, and negative predictive value of FCP (cut‐off level, 425 μg/g) for the prediction of inactive disease (Mayo Score ≤ 2) were 94.3, 88.7, 86.2, and 95.4%, respectively. We also found a FCP cut‐off value of 188 μg/g for the differentiation of UC from IBS‐D. Conclusions The study reveals the large quantitative differences in FCP cut‐off levels in different study populations. This study demonstrates a wide variation in FCP cut‐off levels in the initial diagnosis of UC as well as in follow‐up post‐treatment. Therefore, this test requires validation of the available test kits and finding of appropriate cut‐off levels for different study populations.
Collapse
Affiliation(s)
- Ashish Kumar Jha
- Department of Gastroenterology Indira Gandhi Institute of Medical Sciences Patna India
| | - Madhur Chaudhary
- Department of Gastroenterology Indira Gandhi Institute of Medical Sciences Patna India
| | - Vishwa Mohan Dayal
- Department of Gastroenterology Indira Gandhi Institute of Medical Sciences Patna India
| | - Amarendra Kumar
- Department of Gastroenterology Indira Gandhi Institute of Medical Sciences Patna India
| | - Sanjeev Kumar Jha
- Department of Gastroenterology Indira Gandhi Institute of Medical Sciences Patna India
| | - Praveen Jha
- Department of Gastroenterology Indira Gandhi Institute of Medical Sciences Patna India
| | - Shubham Purkayastha
- Department of Gastroenterology Indira Gandhi Institute of Medical Sciences Patna India
| | - Ravish Ranjan
- Department of Gastroenterology Indira Gandhi Institute of Medical Sciences Patna India
| |
Collapse
|
30
|
Role of fecal calprotectin as a biomarker of intestinal inflammation in ulcerative colitis: a prospective study. REV ROMANA MED LAB 2018. [DOI: 10.2478/rrlm-2018-0006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Abstract
Background: The clinical utility of non-invasive markers in the diagnosis and monitoring of ulcerative colitis (UC) has been intensively studied. The aim of our study was to evaluate the value of fecal calprotectin (FC) in differentiating between UC and irritable bowel syndrome (IBS), and in estimating inflammatory activity in UC.
Method: A total number of 140 patients were included in the study. All patients underwent ileocolonoscopy with biopsies, quantitative determination of FC, and blood tests (white blood cell count, CRP, ESR). The severity of UC was assessed by using the Ulcerative Colitis Disease Activity Index (UCDAI) and Mayo endoscopic score.
Results: In patients with active UC the mean values of FC were 373.8 +/- 146.3 μg/g, significantly higher than those in the inactive UC (mean values 36.04 +/- 13.25 μg/g), and in IBS (42.9 +/- 16.00 μg/g). In univariate regression analysis, elevated FC levels strongly correlated with pancolitis (p=0.0001), UCDAI and Mayo scores (p=0.0001), and elevated CRP levels. In multivariate regression model, FC was positively associated with severe pancolitis, and elevated CRP. The optimal cutoff value of FC for the prediction of severe pancolitis (Mayo score˃ 3) was 540 μg/g. We obtained 71.4% sensitivity (CI95%: 41.95-91.6) and 96.1% specificity (CI95%: 89.2 -99.2) of FC in assessing the severity of inflammation in UC patients.
Conclusion: FC is a promising marker that can be used in clinical practice to select patients with organic intestinal disorders, compared with those with functional disorders. It also correlates very well with the extent of lesions and the severity of clinical symptoms in UC, with increased sensitivity and specificity.
Collapse
|
31
|
Ou G, Bressler B, Galorport C, Lam E, Ko HH, Enns R, Telford J, Schaffer N, Lee T, Rosenfeld G. Rate of Corticosteroid-Induced Mood Changes in Patients with Inflammatory Bowel Disease: A Prospective Study. J Can Assoc Gastroenterol 2018; 1:99-106. [PMID: 31294728 PMCID: PMC6507281 DOI: 10.1093/jcag/gwy023] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Background Corticosteroid is an effective therapeutic option for inflammatory bowel disease flares, but its adverse effects may compromise treatment adherence and reduce patients’ quality of life. There is lack of data on the incidence of corticosteroid-induced mood changes in this patient population, which may be underappreciated by healthcare providers in clinical practice and interfere with optimal care. This study aimed to determine the rate of mood changes in this patient population. Methods In this prospective observational study, adult outpatients treated with prednisone for inflammatory bowel disease flares were considered for inclusion. Participants completed validated questionnaires (Beck Depression Inventory-II and Activation Subscale of Internal State Scale version two) before starting prednisone, after two weeks of prednisone, and at the end of prednisone taper to assess for mood changes. Harvey-Bradshaw Index and Simple Clinical Colitis Activity Index were used to monitor clinical disease activity. Results Fifty-three subjects were included in the analyses. The rate of mood change after two weeks of prednisone was 49.1%, primarily driven by increase in mood towards (hypo)mania. Younger age was an independent risk factor. Mood state returned to pretreatment level at the end of treatment. There was no correlation between clinical disease activity change and mood change. Conclusions Oral prednisone for inflammatory bowel disease flare is associated with high rate of mood change. As prednisone is a critical part of induction therapy, ways to minimize this adverse event must be studied. For now, healthcare providers should inform patients and monitor closely for this adverse event.
Collapse
Affiliation(s)
- George Ou
- University of British Columbia, Faculty of Medicine, Department of Medicine. St. Paul's Hospital, Vancouver, B.C. Canada
| | - Brian Bressler
- University of British Columbia, Faculty of Medicine, Department of Medicine. St. Paul's Hospital, Vancouver, B.C. Canada
| | - Cherry Galorport
- University of British Columbia, Faculty of Medicine, Department of Medicine. St. Paul's Hospital, Vancouver, B.C. Canada
| | - Eric Lam
- University of British Columbia, Faculty of Medicine, Department of Medicine. St. Paul's Hospital, Vancouver, B.C. Canada
| | - Hin Hin Ko
- University of British Columbia, Faculty of Medicine, Department of Medicine. St. Paul's Hospital, Vancouver, B.C. Canada
| | - Robert Enns
- University of British Columbia, Faculty of Medicine, Department of Medicine. St. Paul's Hospital, Vancouver, B.C. Canada
| | - Jennifer Telford
- University of British Columbia, Faculty of Medicine, Department of Medicine. St. Paul's Hospital, Vancouver, B.C. Canada
| | - Nathan Schaffer
- University of British Columbia, Faculty of Medicine, Department of Medicine. St. Paul's Hospital, Vancouver, B.C. Canada
| | - Terry Lee
- University of British Columbia, Faculty of Medicine, Department of Medicine. St. Paul's Hospital, Vancouver, B.C. Canada
| | - Greg Rosenfeld
- University of British Columbia, Faculty of Medicine, Department of Medicine. St. Paul's Hospital, Vancouver, B.C. Canada
| |
Collapse
|
32
|
Vavricka SR, Heinrich H, Buetikofer S, Breitenmoser F, Burri E, Schneider-Yin X, Barman-Aksoezen J, Biedermann L, Scharl M, Zeitz J, Rogler G, Misselwitz B, Sauter M. The Vampire Study: Significant elevation of faecal calprotectin in healthy volunteers after 300 ml blood ingestion mimicking upper gastrointestinal bleeding. United European Gastroenterol J 2018; 6:1007-1014. [PMID: 30228888 DOI: 10.1177/2050640618774416] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2018] [Accepted: 04/04/2018] [Indexed: 12/28/2022] Open
Abstract
Background Faecal calprotectin correlates with histological and clinical activity in inflammatory bowel disease. Gastrointestinal bleeding might also increase faecal calprotectin levels, erroneously implying intestinal inflammation; however, this possibility has not been systematically assessed. Methods Sixteen healthy volunteers without gastrointestinal disease and normal faecal calprotectin baseline values ingested their own blood twice, either by drinking or via nasogastric tube. Quantities of 100 ml and 300 ml blood were ingested in a randomised order, with a 28-day wash-out period. Faecal calprotectin, faecal occult blood test, and the occurrence of melaena were assessed. Faecal calprotectin ≥ 50 µg/g was considered elevated. Results Melaena was reported by all healthy volunteers after 300 ml and by 11/15 healthy volunteers (71%) after 100 ml blood ingestion. One day after ingestion of 300 ml blood, 8/16 faecal calprotectin tests were positive compared to 1/16 at baseline (p = 0.016). Faecal calprotectin levels above > 200 µg/g were rarely observed. There was a trend for faecal calprotectin test positivity also after ingestion of 100 ml. Conclusion Ingestion of blood resulted in an increase in faecal calprotectin-positive tests. Gastrointestinal bleeding should be considered as a potential cause of mild faecal calprotectin elevation > 50 µg/g; however, increased faecal calprotectin above > 250-300 µg/g, the established cut-off for relevant intestinal inflammation in patients with inflammatory bowel disease, is rare.
Collapse
Affiliation(s)
- Stephan R Vavricka
- Department of Medicine, Division of Gastroenterology, Triemli Hospital, Zurich, Switzerland.,Division of Gastroenterology and Hepatology, University Hospital Zurich and University of Zurich, Zurich, Switzerland.,Department of Gastroenterology, St Claraspital, Basel, Switzerland
| | - Henriette Heinrich
- Division of Gastroenterology and Hepatology, University Hospital Zurich and University of Zurich, Zurich, Switzerland.,Department of Gastroenterology, St Claraspital, Basel, Switzerland
| | - Simon Buetikofer
- Department of Medicine, Division of Gastroenterology, Triemli Hospital, Zurich, Switzerland.,Division of Gastroenterology and Hepatology, University Hospital Zurich and University of Zurich, Zurich, Switzerland
| | - Flavia Breitenmoser
- Department of Medicine, Division of Gastroenterology, Triemli Hospital, Zurich, Switzerland
| | - Emanuel Burri
- Department of Gastroenterology, Cantonal Hospital, Liestal, Switzerland
| | | | | | - Luc Biedermann
- Division of Gastroenterology and Hepatology, University Hospital Zurich and University of Zurich, Zurich, Switzerland
| | - Michael Scharl
- Division of Gastroenterology and Hepatology, University Hospital Zurich and University of Zurich, Zurich, Switzerland
| | - Jonas Zeitz
- Division of Gastroenterology and Hepatology, University Hospital Zurich and University of Zurich, Zurich, Switzerland
| | - Gerhard Rogler
- Division of Gastroenterology and Hepatology, University Hospital Zurich and University of Zurich, Zurich, Switzerland
| | - Benjamin Misselwitz
- Division of Gastroenterology and Hepatology, University Hospital Zurich and University of Zurich, Zurich, Switzerland
| | - Matthias Sauter
- Department of Medicine, Division of Gastroenterology, Triemli Hospital, Zurich, Switzerland.,Division of Gastroenterology and Hepatology, University Hospital Zurich and University of Zurich, Zurich, Switzerland.,Department of Gastroenterology, St Claraspital, Basel, Switzerland
| |
Collapse
|
33
|
Heilmann RM, Berghoff N, Mansell J, Grützner N, Parnell NK, Gurtner C, Suchodolski JS, Steiner JM. Association of fecal calprotectin concentrations with disease severity, response to treatment, and other biomarkers in dogs with chronic inflammatory enteropathies. J Vet Intern Med 2018; 32:679-692. [PMID: 29460444 PMCID: PMC5866976 DOI: 10.1111/jvim.15065] [Citation(s) in RCA: 71] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2017] [Revised: 01/01/2018] [Accepted: 01/16/2018] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Calprotectin is a marker of inflammation, but its clinical utility in dogs with chronic inflammatory enteropathies (CIE) is unknown. OBJECTIVE Evaluation of fecal calprotectin in dogs with biopsy-confirmed CIE. ANIMALS 127 dogs. METHODS Prospective case-control study. Dogs were assigned a canine chronic enteropathy clinical activity index (CCECAI) score, and histologic lesions severity was assessed. Fecal calprotectin, fecal S100A12, and serum C-reactive protein (CRP) were measured. Food- or antibiotic-responsive cases (FRE/ARE, n = 13) were distinguished from steroid-/immunosuppressant-responsive or -refractory cases (SRE/IRE, n = 20). Clinical response to treatment in SRE/IRE dogs was classified as complete remission (CR), partial response (PR), or no response (NR). RESULTS Fecal calprotectin correlated with CCECAI (ρ = 0.27, P = .0065) and fecal S100A12 (ρ = 0.90, P < .0001), some inflammatory criteria, and cumulative inflammation scores, but not serum CRP (ρ = 0.16, P = .12). Dogs with SRE/IRE had higher fecal calprotectin concentrations (median: 2.0 μg/g) than FRE/ARE dogs (median: 1.4 μg/g), and within the SRE/IRE group, dogs with PR/NR had higher fecal calprotectin (median: 37.0 μg/g) than dogs with CR (median: 1.6 μg/g). However, both differences did not reach statistical significance (both P = .10). A fecal calprotectin ≥15.2 μg/g separated both groups with 80% sensitivity (95% confidence interval [95%CI]: 28%-100%) and 75% specificity (95%CI: 43%-95%). CONCLUSIONS AND CLINICAL IMPORTANCE Fecal calprotectin could be a useful surrogate marker of disease severity in dogs with CIE, but larger longitudinal studies are needed to evaluate its utility in predicting the response to treatment.
Collapse
Affiliation(s)
- Romy M. Heilmann
- Small Animal ClinicCollege of Veterinary Medicine, University of LeipzigLeipzigSaxonyGermany
- Gastrointestinal LaboratoryCollege of Veterinary Medicine and Biomedical Sciences, Texas A&M UniversityCollege StationTexas
| | - Nora Berghoff
- Gastrointestinal LaboratoryCollege of Veterinary Medicine and Biomedical Sciences, Texas A&M UniversityCollege StationTexas
- Department of Pathobiology & Diagnostic InvestigationCollege of Veterinary Medicine, Michigan State UniversityEast LansingMichigan
| | - Joanne Mansell
- Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical SciencesTexas A&M UniversityCollege StationTexas
| | - Niels Grützner
- Gastrointestinal LaboratoryCollege of Veterinary Medicine and Biomedical Sciences, Texas A&M UniversityCollege StationTexas
- Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle‐WittenbergHalle (Saale)Saxony‐AnhaltGermany
| | - Nolie K. Parnell
- Small Animal Veterinary Teaching Hospital, College of Veterinary Medicine, Purdue UniversityWest LafayetteIndiana
| | - Corinne Gurtner
- Institute of Animal Pathology, Department of Infectious Diseases and PathobiologyVetsuisse Faculty Bern, University of BernBernSwitzerland
- Institute of Veterinary Pathology, College of Veterinary Medicine, Freie Universität BerlinBerlinGermany
| | - Jan S. Suchodolski
- Gastrointestinal LaboratoryCollege of Veterinary Medicine and Biomedical Sciences, Texas A&M UniversityCollege StationTexas
| | - Jörg M. Steiner
- Gastrointestinal LaboratoryCollege of Veterinary Medicine and Biomedical Sciences, Texas A&M UniversityCollege StationTexas
| |
Collapse
|
34
|
Fukunaga S, Kuwaki K, Mitsuyama K, Takedatsu H, Yoshioka S, Yamasaki H, Yamauchi R, Mori A, Kakuma T, Tsuruta O, Torimura T. Detection of calprotectin in inflammatory bowel disease: Fecal and serum levels and immunohistochemical localization. Int J Mol Med 2017; 41:107-118. [PMID: 29115397 PMCID: PMC5746327 DOI: 10.3892/ijmm.2017.3244] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2017] [Accepted: 10/19/2017] [Indexed: 12/21/2022] Open
Abstract
The aim of the present study was to quantify calprotectin levels using an enzyme-linked immunosorbent assay (ELISA) and a point-of-care test (POCT) in patients with inflammatory bowel disease. Overall, 113 patients with ulcerative colitis (UC; 51 men and 62 women) and 42 patients with Crohn's disease (CD; 29 men and 13 women), who were scheduled to undergo a colonoscopy, were prospectively enrolled and scored endoscopically and clinically. An additional 96 healthy, age-matched subjects served as the normal controls. Feces and blood samples from the patients with UC and CD, and the normal controls were analyzed. These patients had received adequate medical treatment. The tissue distribution of calprotectin was investigated using immunohistochemistry. The fecal calprotectin levels, as measured using an ELISA, were correlated with the endoscopic and clinical disease activities and laboratory parameters, including serum levels of hemoglobin (Hb), albumin and C-reactive protein, and erythrocyte sedimentation rate, particularly among the patients with UC. The fecal Hb level was close to that of the fecal calprotectin level (r=0.57; P<0.0001). The fecal calprotectin level measured using an ELISA was well-correlated with the fecal calprotectin level measured using the POCT (r=0.81; P<0.0001), but was not correlated with the serum calprotectin level (r=0.1013; P=0.47). An immunohistochemical investigation revealed that patients with both UC and CD had higher neutrophil and monocyte/macrophage calprotectin-positive cell expression levels, compared with those in the normal controls. Fecal calprotectin was considered a reliable marker for disease activity, and the assessment of fecal calprotectin via POCT showed potential as a rapid and simple measurement in clinical settings.
Collapse
Affiliation(s)
- Shuhei Fukunaga
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan
| | - Kotaro Kuwaki
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan
| | - Keiichi Mitsuyama
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan
| | - Hidetoshi Takedatsu
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan
| | - Shinichiro Yoshioka
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan
| | - Hiroshi Yamasaki
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan
| | - Ryosuke Yamauchi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan
| | - Atsushi Mori
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan
| | - Tatsuyuki Kakuma
- Department of Biostatistics Center, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan
| | - Osamu Tsuruta
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan
| | - Takuji Torimura
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan
| |
Collapse
|
35
|
Rapid Fecal Calprotectin Test and Symptom Index in Monitoring the Disease Activity in Colonic Inflammatory Bowel Disease. Dig Dis Sci 2017; 62:3123-3130. [PMID: 28948412 DOI: 10.1007/s10620-017-4770-0] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2017] [Accepted: 09/16/2017] [Indexed: 12/13/2022]
Abstract
BACKGROUND Fecal calprotectin is a reliable surrogate marker for inflammatory activity in inflammatory bowel disease (IBD). AIMS For the noninvasive monitoring of the activity of colonic inflammation, we validated a symptom index suitable for ulcerative colitis and colonic Crohn's disease. By combining the symptom index with a rapid semi-quantitative calprotectin test, we constructed a new activity index based on the highest AUCs, using histological remission as a reference. We also evaluated the correlation of the patient-reported influence of the IBD in the daily life, measured by a VAS, with the inflammation activity. METHODS The disease activity of 72 patients with IBD of the colon was determined by endoscopic activity scores (SES-CD/UCEIS). The patients provided stool samples for determination of calprotectin and filled in a questionnaire about their symptoms during the last week. RESULTS The results of the symptom index demonstrated a statistically significant correlation with the rapid calprotectin test, histological inflammation activity, and the VAS. No correlations were found between the VAS and calprotectin or the histological inflammation activity. The sensitivity of the combination index to detect active inflammation was slightly superior to fecal calprotectin alone. CONCLUSION The new symptom index and the combination index are simple, noninvasive means for distinguishing remission from active inflammation in colonic IBD. With the VAS, we can pick up patients who need psychosocial support because of the disease burden, even if their IBD is in remission.
Collapse
|
36
|
Lee SH, Kim MJ, Chang K, Song EM, Hwang SW, Park SH, Yang DH, Kim KJ, Byeon JS, Myung SJ, Yang SK, Ye BD. Fecal calprotectin predicts complete mucosal healing and better correlates with the ulcerative colitis endoscopic index of severity than with the Mayo endoscopic subscore in patients with ulcerative colitis. BMC Gastroenterol 2017; 17:110. [PMID: 29061121 PMCID: PMC5654142 DOI: 10.1186/s12876-017-0669-7] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2017] [Accepted: 10/15/2017] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND We aimed to evaluate the role of fecal calprotectin (FC) as a noninvasive marker for the disease activity of ulcerative colitis (UC) in a Korean cohort. METHODS A total of 181 fecal samples were collected from 181 consecutive UC patients between April 2015 and September 2016. FC levels were measured using the Quantum Blue® Calprotectin rapid test. The laboratory test results, partial Mayo Score (pMS), and colonoscopic imaging findings at FC level measurement were retrospectively reviewed. The Mayo endoscopic subscore (MES) and UC endoscopic index of severity (UCEIS) were graded by 2 certified endoscopists after training with 50 other cases. RESULTS The FC levels were significantly correlated with pMS (Spearman correlation coefficient r = 0.428, p < 0.001), MES (r = 0.304, p < 0.001), UCEIS (r = 0.430, p < 0.001), and CRP (r = 0.379, p < 0.001). FC levels exhibited a significantly better correlation with UCEIS than with MES (Meng's z = - 2.457, p = 0.01). The FC cut-off level of 187.0 mg/kg indicated complete mucosal healing (MES = 0; UCEIS =0) with a sensitivity and specificity of 0.857 and 0.891, respectively (area under the curve, 0.883; 95% confidence interval, 0.772-1.000). CONCLUSION The FC level is significantly correlated with the clinical disease activity index, endoscopic indices, and serum inflammatory biomarkers in a Korean UC cohort. FC is highly predictive of complete mucosal healing in UC. UCEIS exhibits a stronger correlation with the FC level, as compared to MES. Thus, FC could be used as a reliable noninvasive indicator for evaluating disease activity and mucosal healing in UC.
Collapse
Affiliation(s)
- Sun-Ho Lee
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
| | - Min-Ju Kim
- Department of Clinical Epidemiology and Biostatistics, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
| | - Kiju Chang
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
| | - Eun Mi Song
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
| | - Sung Wook Hwang
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea.,Inflammatory Bowel Disease Center, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
| | - Sang Hyoung Park
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea.,Inflammatory Bowel Disease Center, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
| | - Dong-Hoon Yang
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
| | - Kyung-Jo Kim
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea.,Inflammatory Bowel Disease Center, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
| | - Jeong-Sik Byeon
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
| | - Seung-Jae Myung
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
| | - Suk-Kyun Yang
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea.,Inflammatory Bowel Disease Center, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
| | - Byong Duk Ye
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea. .,Inflammatory Bowel Disease Center, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea.
| |
Collapse
|
37
|
Alrefai D, Jones J, El-Matary W, Whiting SJ, Aljebreen A, Mirhosseini N, Vatanparast H. The Association of Vitamin D Status with Disease Activity in a Cohort of Crohn's Disease Patients in Canada. Nutrients 2017; 9:nu9101112. [PMID: 29023388 PMCID: PMC5691728 DOI: 10.3390/nu9101112] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2017] [Revised: 09/28/2017] [Accepted: 10/06/2017] [Indexed: 02/07/2023] Open
Abstract
We determined the association between vitamin D status as 25hydroxyvitamin D [25(OH)D] and disease activity in a cohort of 201 Crohn’s Disease (CD) patients in Saskatoon, Canada over three years. The association between high-sensitivity C-reactive protein (hs-CRP) and 25(OH)D and several disease predictors were evaluated by the generalized estimating equation (GEE) over three time-point measurements. A GEE binary logistic regression test was used to evaluate the association between vitamin D status and the Harvey-Bradshaw Index (HBI). The deficient vitamin D group (≤29 nmol/L) had significantly higher mean hs-CRP levels compared with the three other categories of vitamin D status (p < 0.05). CRP was significantly lower in all of the other groups compared with the vitamin D-deficient group, which had Coef. = 12.8 units lower (95% CI −19.8, −5.8), Coef. 7.85 units (95% CI −14.9, −0.7), Coef. 9.87 units (95% CI −17.6, −2.0) for the vitamin D insufficient, adequate, and optimal groups, respectively. The vitamin D status was associated with the HBI active disease category. However, the difference in the odds ratio compared with the reference category of deficient vitamin D category was only significant in the insufficient category (odds ratio = 3.45, p = 0.03, 95% CI 1.0, 10.8). Vitamin D status was inversely associated with indicators of disease activity in Crohn’s disease, particularly with the objective measures of inflammation.
Collapse
Affiliation(s)
- Dania Alrefai
- College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5C9, Canada.
| | - Jennifer Jones
- Division of Digestive Care & Endoscopy, Department of Community Health and Epidemiology, Dalhousie University, Truro, NS B2N 5E3, Canada.
| | - Wael El-Matary
- College of Medicine, University of Manitoba, Winnipeg, MB R3T 2N2, Canada.
| | - Susan J Whiting
- College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5C9, Canada.
| | | | | | - Hassan Vatanparast
- College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5C9, Canada.
| |
Collapse
|
38
|
Pepper RJ, Draibe JB, Caplin B, Fervenza FC, Hoffman GS, Kallenberg CGM, Langford CA, Monach PA, Seo P, Spiera R, William St Clair E, Tchao NK, Stone JH, Specks U, Merkel PA, Salama AD. Association of Serum Calprotectin (S100A8/A9) Level With Disease Relapse in Proteinase 3-Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. Arthritis Rheumatol 2017; 69:185-193. [PMID: 27428710 DOI: 10.1002/art.39814] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2015] [Accepted: 07/07/2016] [Indexed: 02/01/2023]
Abstract
OBJECTIVE S100A8/A9 (calprotectin) has shown promise as a biomarker for predicting relapse in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). This study was undertaken to investigate serum S100A8/A9 level as a biomarker for predicting future relapse in a large cohort of patients with severe AAV. METHODS Serum levels of S100A8/A9 were measured at baseline and months 1, 2, and 6 following treatment initiation in 144 patients in the Rituximab in ANCA-Associated Vasculitis trial (cyclophosphamide/azathioprine versus rituximab [RTX] for induction of remission) in whom complete remission was attained. RESULTS Patients were divided into 4 groups: proteinase 3 (PR3)-ANCA with relapse (n = 37), PR3-ANCA without relapse (n = 56), myeloperoxidase (MPO)-ANCA with relapse (n = 6), and MPO-ANCA without relapse (n = 45). Serum S100A8/A9 level decreased in all groups during the first 6 months of treatment. The percentage reduction from baseline to month 2 was significantly different between patients who experienced a relapse and those who did not in the PR3-ANCA group (P = 0.046). A significantly higher risk of relapse was associated with an increase in S100A8/A9 level between baseline and month 2 (P = 0.0043) and baseline and month 6 (P = 0.0029). Subgroup analysis demonstrated that patients treated with RTX who had increased levels of S100A8/A9 were at greatest risk of future relapse (P = 0.028). CONCLUSION An increase in serum S100A8/A9 level by month 2 or 6 compared to baseline identifies a subgroup of PR3-ANCA patients treated with RTX who are at higher risk of relapse by 18 months. Since RTX is increasingly used for remission induction in PR3-ANCA-positive patients experiencing a relapse, S100A8/A9 level may assist in identifying those patients requiring more intensive or prolonged treatment.
Collapse
Affiliation(s)
- Ruth J Pepper
- University College London Centre for Nephrology, Royal Free Hospital, London, UK
| | - Juliana B Draibe
- University College London Centre for Nephrology, Royal Free Hospital, London, UK
| | - Ben Caplin
- University College London Centre for Nephrology, Royal Free Hospital, London, UK
| | | | | | | | | | | | - Philip Seo
- Johns Hopkins University, Baltimore, Maryland
| | | | | | | | | | | | | | - Alan D Salama
- University College London Centre for Nephrology, Royal Free Hospital, London, UK
| | | |
Collapse
|
39
|
Lee J. [Fecal Calprotectin in Inflammatory Bowel Disease]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2017; 67:233-7. [PMID: 27206433 DOI: 10.4166/kjg.2016.67.5.233] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Inflammatory bowel disease (IBD), Crohn's disease and ulcerative colitis comprise conditions characterized by chronic, relapsing immune activation and inflammation within the gastrointestinal tract. Objective estimation of intestinal inflammation is the mainstay in the diagnosis and observation of IBD, but is primarily dependent on expensive and invasive procedures such as endoscopy. Therefore, a simple, noninvasive, inexpensive, and accurate test would be extremely important in clinical practice. Fecal calprotectin is a calcium-containing protein released into the lumen that is excreted in feces during acute and chronic inflammation. It is well-researched, noninvasive, and has high sensitivity and specificity for identification of inflammation in IBD. This review will focus on the use of fecal calprotectin to help diagnose, monitor, and determine treatment in IBD.
Collapse
Affiliation(s)
- Jun Lee
- Department of Internal Medicine, College of Medicine, Chosun University, Gwangju, Korea
| |
Collapse
|
40
|
Abstract
Over the last thirty years knowledge on fecal biomarkers (FM) has substantially increased. Nowadays these non-invasive inflammation markers are used in the daily management of inflammatory bowel disease (IBD). The interest in investigating FM was motivated by the need of a simple, quick, disposable and less invasive marker of disease activity, which might remove the need for endoscopy when following up with patients. Areas covered: Current literature was reviewed for articles regarding the role of FM in IBD diagnosis, activity, flare prediction, medication and surgical treatment response as well as how FM may differ in adult and paediatric IBD patient populations. Expert commentary: Although FM is relevant in IBD patient follow-up, there isn't enough data regarding FM reference values for different ages, different disease subtypes, disease localization/extension or response to therapy. Serial measurements of FM for each patient may be useful in accessing relapse in most patients. FM presented more consistent results when used as a predictive tool of relapse after ileocecal surgery in Crohn's disease. Ongoing research will clarify FM role in decision-making IBD daily practice.
Collapse
Affiliation(s)
- Paula Ministro
- a Gastroenterology Department , Tondela - Viseu Hospital Center , Viseu , Portugal
| | - Diana Martins
- a Gastroenterology Department , Tondela - Viseu Hospital Center , Viseu , Portugal
| |
Collapse
|
41
|
Use of Intestinal Ultrasound to Monitor Crohn's Disease Activity. Clin Gastroenterol Hepatol 2017; 15:535-542.e2. [PMID: 27856365 DOI: 10.1016/j.cgh.2016.10.040] [Citation(s) in RCA: 146] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2016] [Accepted: 10/27/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS We performed a multicenter study to determine whether transabdominal bowel wall ultrasonography, a noninvasive procedure that does not require radiation, can be used to monitor progression of Crohn's disease (CD). METHODS We performed a 12-month prospective, noninterventional study at 47 sites in Germany, from December 2010 through September 2014. Our study included 234 adult patients with CD who experienced a flare, defined as Harvey-Bradshaw index score of ≥7. All patients received treatment intensification, most with tumor necrosis factor antagonists. Ultrasound parameters and clinical data were assessed at baseline and then after 3, 6, and 12 months. The primary endpoint was the change in ultrasound parameters within 12 months of study enrollment. RESULTS All patients included had bowel wall alterations either within the terminal ileum and/or segments of the colon. After 3 and 12 months, ultrasonographic examination showed significant improvements of nearly all ultrasound parameters, including reductions in bowel wall thickening or stratification, decreased fibrofatty proliferation, and increased signals in color Doppler ultrasound (P < .01 for all parameters at months 3 and 12). Median Harvey-Bradshaw index scores decreased from 10 at baseline to 2 after 12 months. Improvement in bowel wall thickness correlated with reduced levels of C-reactive protein after 3 months (P ≤ .001). CONCLUSIONS In a multicenter prospective study, we found that ultrasonographic examination can be used to monitor disease activity in patients with active CD. Bowel ultrasonography seems to be an ideal follow-up method to evaluate early transmural changes in disease activity, in response to medical treatment. German Clinical Trials Register: drks.de/DRKS00010805.
Collapse
|
42
|
Pediatric Crohn Disease Clinical Outcome Assessments and Biomarkers: Current State and Path Forward for Global Collaboration. J Pediatr Gastroenterol Nutr 2017; 64:368-372. [PMID: 27253661 DOI: 10.1097/mpg.0000000000001284] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE There is a pressing need for drug development in pediatric Crohn disease (CD). Our aim was to provide strategic approaches toward harmonization of current thinking about clinical outcome assessments (COAs) and biomarkers to facilitate drug development in pediatric CD. METHODS Scientists from the United States Food and Drug Administration, European Medicines Agency, Health Canada, and the Pharmaceuticals and Medical Devices Agency of Japan had monthly teleconferences from January 2014 through May 2015. A literature review was conducted to assess the measurement properties of all existing COA tools and to evaluate the current landscape of biomarkers used in pediatric CD. Based on the findings of literature review, we reached the consensus on the strategic approaches for evaluating outcomes in pediatric CD trials. RESULTS The pediatric Crohn's Disease Activity Index, Crohn's Disease Activity Index, and Harvey-Bradshaw's index were used in pediatric CD clinical studies. But they lack adequate measurement properties (validity, reliability, and ability to detect change of the treatment) that are required to support approval of products intended to treat pediatric CD. Biomarkers (ie, fecal lactoferrin, osteoprotegerin, and calprotectin) have shown some promise for their potential as noninvasive surrogate endpoints in CD. CONCLUSIONS Lack of well-defined and reliable COAs presents a hurdle for global drug development in pediatric CD. It is essential to develop well-defined and reliable COAs that can measure meaningful clinical benefit for patients in terms of how they feel, function, and survive. Development of noninvasive biomarkers as reliable surrogate endpoints needs to be further explored.
Collapse
|
43
|
Yamamoto-Furusho J, Bosques-Padilla F, de-Paula J, Galiano M, Ibañez P, Juliao F, Kotze P, Rocha J, Steinwurz F, Veitia G, Zaltman C. Diagnosis and treatment of inflammatory bowel disease: First Latin American Consensus of the Pan American Crohn's and Colitis Organisation. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2017. [DOI: 10.1016/j.rgmxen.2016.07.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
|
44
|
Yamamoto-Furusho J, Bosques-Padilla F, de-Paula J, Galiano M, Ibañez P, Juliao F, Kotze P, Rocha J, Steinwurz F, Veitia G, Zaltman C. Diagnóstico y tratamiento de la enfermedad inflamatoria intestinal: Primer Consenso Latinoamericano de la Pan American Crohn's and Colitis Organisation. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2017; 82:46-84. [PMID: 27979414 DOI: 10.1016/j.rgmx.2016.07.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/20/2016] [Revised: 06/23/2016] [Accepted: 07/06/2016] [Indexed: 02/08/2023]
|
45
|
Interpreting Registrational Clinical Trials of Biological Therapies in Adults with Inflammatory Bowel Diseases. Inflamm Bowel Dis 2016; 22:2711-2723. [PMID: 27585411 DOI: 10.1097/mib.0000000000000909] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND The use of biologics to treat inflammatory bowel disease is supported by robust randomized controlled trials in both ulcerative colitis and Crohn's disease. Nonetheless, an understanding of the principles of clinical trial design is necessary to extrapolate study findings to clinical practice. METHODS We conducted a review of inflammatory bowel disease registrational clinical trials of biologics to determine how differences in trial design potentially influence results and interpretation. RESULTS Registrational trials of biological agents have used diverse patient populations, outcome measures, and designs, which makes comparisons of results among studies difficult. Key differences among trials include patient populations, choice of symptom-based measures or objective outcomes as endpoints, and overall trial design. Additional factors, including analytical methods, can also influence the interpretation of outcomes. CONCLUSIONS The most robust evidence is derived from comparative effectiveness trials. In the absence of these, clinicians should be aware of the various methodological issues which could impact interpretation of efficacy and safety outcomes, including differences in patient population, study design, and analytic methodology.
Collapse
|
46
|
Puolanne AM, Kolho KL, Alfthan H, Ristimäki A, Mustonen H, Färkkilä M. Rapid faecal tests for detecting disease activity in colonic inflammatory bowel disease. Eur J Clin Invest 2016; 46:825-32. [PMID: 27438629 DOI: 10.1111/eci.12660] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2016] [Accepted: 07/17/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND Increasing numbers of patients with inflammatory bowel disease (IBD) have raised the need for a rapid noninvasive means to monitor disease activity. We validated two rapid tests for faecal calprotectin and one for faecal lactoferrin and compared them to the most common clinical and endoscopic scores, enzyme-linked immunosorbent assay (ELISA) calprotectin test and systemic inflammation markers. MATERIALS AND METHODS The clinical and endoscopic disease activity of 72 patients with colonic IBD, who underwent ileocolonoscopy, was determined. The patients provided stool samples to measure calprotectin and lactoferrin, and blood samples to measure systemic inflammation markers. RESULTS Rapid calprotectin tests correlated significantly with clinical and endoscopic indices and standard ELISA calprotectin in ulcerative colitis, but not in Crohn's disease. CalDetect correlated more closely with ELISA calprotectin than CerTest FC in concentrations exceeding 200 μg/g. CalDetect was also more sensitive in indicating histological remission or mild disease than was CerTest FC at cut-off of 200 μg/g. CerTest Lactoferrin was comparable to CalDetect in their correlation with clinical, endoscopic and histological scores. CONCLUSIONS These rapid tests are suitable for identifying patients with inactive or mildly active disease, but as semiquantitative or qualitative tests, they cannot totally replace ELISA calprotectin in decision-making related to therapy.
Collapse
Affiliation(s)
- Anna-Maija Puolanne
- Division of Gastroenterology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.
| | - Kaija-Leena Kolho
- Children's Hospital, Helsinki University Central Hospital, Helsinki, Finland
| | - Henrik Alfthan
- Department of Clinical Chemistry, University of Helsinki, Helsinki, Finland
| | - Ari Ristimäki
- Department of Pathology, HUSLAB and Haartman Institute, Helsinki University Central Hospital, Helsinki, Finland
| | - Harri Mustonen
- Department of Surgery, Biomedicum Helsinki, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland
| | - Martti Färkkilä
- Division of Gastroenterology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
| |
Collapse
|
47
|
Taleban S, Stewart KO, Li DK, Singh P, Pardi DS, Sturgeon HC, Yajnik V, Xavier RJ, Ananthakrishnan AN, Khalili H. Clinical Activity and Quality of Life Indices Are Valid Across Ulcerative Colitis But Not Crohn's Disease Phenotypes. Dig Dis Sci 2016; 61:2627-35. [PMID: 27142671 PMCID: PMC4982770 DOI: 10.1007/s10620-016-4180-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Accepted: 04/20/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND Clinical activity and quality of life (QOL) indices assess disease activity in Crohn's disease (CD) and ulcerative colitis (UC). However, a paucity of data exists on the validity of these indices according to disease characteristics. AIMS To examine the correlation between QOL and clinical activity indices and endoscopic disease activity according to disease characteristics. METHODS We used a prospective registry to identify CD and UC patients ≥18 years old with available information on Short Inflammatory Bowel Disease Questionnaire scores (SIBDQ), Harvey-Bradshaw Index (HBI) and simple endoscopic scores for CD (SES-CD), and Simple Clinical Colitis Activity Index (SCCAI) and Mayo endoscopic score for UC. We used Spearman rank correlations to calculate correlations between indices and Fisher transformation to compare correlations across disease characteristics. RESULTS Among 282 CD patients, we observed poor correlation between clinical activity and QOL indices to SES-CD with no differences in correlation according to disease characteristics. Conversely, among 226 UC patients, clinical activity and QOL had good correlation to Mayo endoscopic score (r = 0.55 and -0.56, respectively) with better correlations observed with left-sided versus extensive colitis (r = 0.73 vs. 0.45, p = 0.005) and shorter duration of disease (r = 0.61 vs. 0.37, p = 0.04). CONCLUSIONS Our data suggest good correlation between SCCAI and endoscopic disease activity in UC, particularly in left-sided disease. Poor correlations between HBI or SIBDQ and SES-CD appear to be consistent across different disease phenotypes.
Collapse
Affiliation(s)
- Sasha Taleban
- Division of Gastroenterology, University of Arizona College of Medicine, Tucson, AZ, 85724, USA.
- Department of Medicine, University of Arizona Center of Aging, Tucson, AZ, 85724, USA.
- Section of Gastroenterology, Banner University Medical Center, 1501 N. Campbell Ave, Tucson, AZ, 85724, USA.
| | - Kathleen O Stewart
- Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA
| | - Darrick K Li
- Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA
| | - Prashant Singh
- Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA
| | - Darrell S Pardi
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Holly C Sturgeon
- Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA
| | - Vijay Yajnik
- Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA
| | - Ramnik J Xavier
- Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA
- The Broad Institute, Cambridge, MA, 02124, USA
- Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA, 02114, USA
| | - Ashwin N Ananthakrishnan
- Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA
| | - Hamed Khalili
- Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
- Crohn's and Colitis Center, Massachusetts General Hospital, 165 Cambridge Street, 9th Floor, Boston, MA, 02114, USA.
| |
Collapse
|
48
|
Cappello M, Morreale GC. The Role of Laboratory Tests in Crohn's Disease. CLINICAL MEDICINE INSIGHTS. GASTROENTEROLOGY 2016; 9:51-62. [PMID: 27656094 PMCID: PMC4991576 DOI: 10.4137/cgast.s38203] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/31/2016] [Revised: 07/12/2016] [Accepted: 07/16/2016] [Indexed: 02/07/2023]
Abstract
In the past, laboratory tests were considered of limited value in Crohn's disease (CD). In the era of biologics, laboratory tests have become essential to evaluate the inflammatory burden of the disease (C-reactive protein, fecal calprotectin) since symptoms-based scores are subjective, to predict the response to pharmacological options and the risk of relapse, to discriminate CD from ulcerative colitis, to select candidates to anti-tumor necrosis factors [screening tests looking for hepatitis B virus and hepatitis C virus status and latent tuberculosis], to assess the risk of adverse events (testing for thiopurine metabolites and thiopurine-methyltransferase activity), and to personalize and optimize therapy (therapeutic drug monitoring). Pharmacogenetics, though presently confined to the assessment of thiopurineme methyltransferase polymorphisms and hematological toxicity associated with thiopurine treatment, is a promising field that will contribute to a better understanding of the molecular mechanisms of the variability in response to the drugs used in CD with the attempt to expand personalized care and precision medicine strategies.
Collapse
Affiliation(s)
- Maria Cappello
- Senior Registrar in Gastroenterology, Gastroenterology and Hepatology Section, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo School of Medicine, Palermo, Italy
| | - Gaetano Cristian Morreale
- Trainee in Gastroenterology, Gastroenterology and Hepatology Section, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo School of Medicine, Palermo, Italy
| |
Collapse
|
49
|
Ikhtaire S, Shajib MS, Reinisch W, Khan WI. Fecal calprotectin: its scope and utility in the management of inflammatory bowel disease. J Gastroenterol 2016; 51:434-46. [PMID: 26897740 DOI: 10.1007/s00535-016-1182-4] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2015] [Accepted: 02/04/2016] [Indexed: 02/07/2023]
Abstract
Gastrointestinal symptoms such as abdominal pain, dyspepsia, and diarrhea are relatively nonspecific and a common cause for seeking medical attention. To date, it is challenging for physicians to differentiate between functional and organic gastrointestinal conditions and it involves the use of serological and endoscopic techniques. Therefore, a simple, noninvasive, inexpensive, and effective test would be of utmost importance in clinical practice. Fecal calprotectin (FC) is considered to be a reliable biomarker that fulfills these criteria. FC can detect intestinal inflammation, and its level correlates well with macroscopic and histological inflammation as detected by colonoscopy and biopsies, respectively. FC has a decent diagnostic accuracy for differentiating organic diseases and functional disorders because of its excellent negative predictive value in ruling out inflammatory bowel disease (IBD) in symptomatic undiagnosed patients. There is accumulating evidence that FC has been effectively used to monitor the natural course of IBD, to predict relapse, and to see the response to treatment. This novel biomarker has the ability to assess mucosal healing (MH), which is a therapeutic goal in IBD management. A literature search was carried out using PubMed with the keywords FC, IBD, intestinal inflammation, and MH. In our review, we provide an overview of the utility and scope of FC as a biomarker in patients with IBD as well as undiagnosed patients with lower gastrointestinal symptoms.
Collapse
Affiliation(s)
- Shapur Ikhtaire
- Department of Pathology and Molecular Medicine, McMaster University, Room 3N7, HSC, 1280 Main Street West, Hamilton, ON, L8S 1R7, Canada
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Mohammad Sharif Shajib
- Department of Pathology and Molecular Medicine, McMaster University, Room 3N7, HSC, 1280 Main Street West, Hamilton, ON, L8S 1R7, Canada
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Walter Reinisch
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
- Division of Gastroenterology, Department of Medicine, McMaster University, Hamilton, ON, Canada
| | - Waliul Islam Khan
- Department of Pathology and Molecular Medicine, McMaster University, Room 3N7, HSC, 1280 Main Street West, Hamilton, ON, L8S 1R7, Canada.
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada.
| |
Collapse
|
50
|
Li Z, Long Y, Bai M, Li J, Feng Z. Neutrophil and Eosinophil Granule Proteins as Potential Biomarkers of Assessing Disease Activity and Severity in Patients With Ulcerative Colitis. J Clin Lab Anal 2016; 30:776-8. [PMID: 27076259 DOI: 10.1002/jcla.21937] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2015] [Accepted: 12/28/2015] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Colonoscopy can assess disease activity and severity of ulcerative colitis (UC) accurately, but it is invasive and costly. Role of noninvasive biomarkers of intestinal inflammation in evaluation of patients with UC is not well understood. In this study, we assessed fecal eosinophil cationic protein (FECP), fecal myeloperoxidase (FMPO), and fecal calprotectin (FC) as surrogate markers of disease activity and severity in patients with UC, and then evaluated effect of the combination of these markers. METHODS Sixty-three UC patients and 59 cases of age-matched controls were investigated. All patients underwent clinical, endoscopic, and histological assessment for disease activity and severity. Fecal samples were analyzed for FECP, FC, and FMPO. RESULTS All three fecal biomarkers were elevated in patients compared with controls (P = 0.000). Significant differences were found between inactive UC and controls (P = 0.000). Cases with severe UC had significantly higher FECP levels than those with mild UC (p < 0.05), but there were no significant differences in FC and FMPO levels among disease severity groups. All three biomarkers showed positive correlation with Ulcerative Colitis Activity Index (UCAI). The areas under the ROC curve of FECP, FC, and FMPO were 0.939, 0.783, and 0.785, respectively. Sensitivity and specificity of fecal biomarkers in assessing disease activity were FECP-88.46%, 89.47%; FC-80.77%, 68.42%; and FMPO-84.62%, 63.16%. CONCLUSIONS All three fecal biomarkers could be used as surrogate markers for assessing disease activity of UC, and FECP provided superior discrimination than FMPO and FC. Moreover, FECP could distinguish between mild disease and severe disease group.
Collapse
Affiliation(s)
- Zhiyan Li
- Department of Clinical Laboratory, Peking University First Hospital, Beijing, China
| | - Yan Long
- Department of Clinical Laboratory, Peking University First Hospital, Beijing, China
| | - Mingjian Bai
- Department of Clinical Laboratory, Peking University First Hospital, Beijing, China
| | - Junxia Li
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Zhenru Feng
- Department of Clinical Laboratory, Peking University First Hospital, Beijing, China.
| |
Collapse
|